Youzhny started the 2004 season with a second round defeat by Sargis Sargsian at the Qatar Open in Doha.
At the Australian Open, Youzhny lost in the first round to Sébastien Grosjean, but then reached his first quarterfinals of the season at the Indesit ATP Milan Indoor, where he lost to Antony Dupuis.
At the Dubai Tennis Championships, he reached his first semifinal of the season after defeating world No.
3 Guillermo Coria in the first round, but lost to Feliciano Lopez in three sets.
At the Indian Wells Masters Youzhny beat Mark Philippoussis in the second round, but lost to world No.
5 Andre Agassi in straight sets in round four.
At the Hamburg Masters, Youzhny reached his first quarterfinals at an ATP Masters 1000 event.
He lost to Ivan Ljubičić in a three setter.
His good form continued into the French Open, where he had wins over Dennis van Scheppingen and Andrei Pavel, but was eliminated in the third round by Nicolas Escude in four sets.

Coming to Wimbledon, Youzhny had won only 2 grass matches and he was upset in the first round by 415 ranked Goran Ivanisevic.
At the 2004 Summer Olympics in Athens, Youzhny upset Nicolas Kiefer to reach the quarterfinals, but lost to American Mardy Fish in straight sets.
His next tournament was the US Open, where he defeated Albert Montañés and David Nalbandian, before losing to Tomas Berdych in five sets.
He responded to his US Open loss by reaching the final of the China Open in Beijing, defeating three top 20 players; Rainer Schüttler, Dominik Hrbatý and Paradorn Srichaphan.
Marat Safin, a fellow Russian, defeated Youzhny in the final.
Youzhny's next two events were the Grand Prix de Tennis de Lyon and the Kremlin Cup, where he reached the quarterfinals, losing to Xavier Malisse, and the semifinals, losing to Nikolay Davydenko, respectively.
In October at the St. Petersburg Open, Youzhny won his first title since 2002, defeating world No.
53 Karol Beck in two sets.
Youzhny ended the year by reaching the quarterfinals of the BNP Paribas Masters in Paris.
He had earlier upset eighth ranked Tim Henman but lost in the quarterfinals to Radek Štěpánek.
Youzhny's season tally was a 42–27 win-loss record, and he had a year-end ranking of sixteen.

The 2005 season started with a first round loss to Rafael Nadal at Qatar ExxonMobil Open.
At the Australian Open, Youzhny was seeded 15th but lost in a five-setter in the second round to Nadal.
Nadal saved a match point in the fourth set.
At the Dubai Tennis Championships, Youzhny reached the quarterfinals and lost to world No.
1 Roger Federer.
Youzhny lost in either the first or second round in six tournaments in a row, including the French Open, where he lost to Jürgen Melzer in three sets.
At Wimbledon, Youzhny, reached the fourth round for the first time since 2002, losing to Fernando González in three sets.
In July, at both the Swedish Open and the Generali Open, Youzhny reached the quarterfinals, losing to Tommy Robredo and Gastón Gaudio respectively.
At the Western & Southern Financial Group Masters in Cincinnati, Youzhny reached his only ATP Masters 1000 quarterfinals of the season, but lost to 5th ranked Andy Roddick in three sets.
After wins against Florian Mayer and Jonas Björkman at the 2005 US Open Youzhny lost in round three to Xavier Malisse, after leading 2–0 in sets.
After a third round loss to Guillermo Coria at the China Open, Youzhny reached the quarterfinals of the Kremlin Cup where he was upset by wild card entry Dmitry Tursunov.
In his last tournament of the season, Youzhny lost his title at the St. Petersburg Open, losing to Robin Vik in the quarterfinals.
Youzhny ended the season with a 23–23 win-loss record, making it one of his worst seasons in his career, and ended the year as world No.
43.

January 2006 started with victories against Jonas Björkman and Davide Sanguinetti, but a quarterfinal loss to Tommy Haas at the Qatar Open This was followed by a first round defeat by Xavier Malisse at the Australian Open.
However, Youzhny steadily improved by reaching the quarterfinals of the PBS Zabreb Indoors and then the semi
Youzhny started the 2004 season with a second round defeat by Sargis Sargsian at the Qatar Open in Doha. At the Australian Open, Youzhny lost in the first round to Sébastien Grosjean, but then reached his first quarterfinals of the season at the Indesit ATP Milan Indoor, where he lost to Antony Dupuis. At the Dubai Tennis Championships, he reached his first semifinal of the season after defeating world No. 3 Guillermo Coria in the first round, but lost to Feliciano Lopez in three sets. At the Indian Wells Masters Youzhny beat Mark Philippoussis in the second round, but lost to world No. 5 Andre Agassi in straight sets in round four. At the Hamburg Masters, Youzhny reached his first quarterfinals at an ATP Masters 1000 event. He lost to Ivan Ljubičić in a three setter. His good form continued into the French Open, where he had wins over Dennis van Scheppingen and Andrei Pavel, but was eliminated in the third round by Nicolas Escude in four sets.
Coming to Wimbledon, Youzhny had won only 2 grass matches and he was upset in the first round by 415 ranked Goran Ivanisevic. At the 2004 Summer Olympics in Athens, Youzhny upset Nicolas Kiefer to reach the quarterfinals, but lost to American Mardy Fish in straight sets. His next tournament was the US Open, where he defeated Albert Montañés and David Nalbandian, before losing to Tomas Berdych in five sets. He responded to his US Open loss by reaching the final of the China Open in Beijing, defeating three top 20 players; Rainer Schüttler, Dominik Hrbatý and Paradorn Srichaphan. Marat Safin, a fellow Russian, defeated Youzhny in the final. Youzhny's next two events were the Grand Prix de Tennis de Lyon and the Kremlin Cup, where he reached the quarterfinals, losing to Xavier Malisse, and the semifinals, losing to Nikolay Davydenko, respectively. In October at the St. Petersburg Open, Youzhny won his first title since 2002, defeating world No. 53 Karol Beck in two sets. Youzhny ended the year by reaching the quarterfinals of the BNP Paribas Masters in Paris. He had earlier upset eighth ranked Tim Henman but lost in the quarterfinals to Radek Štěpánek. Youzhny's season tally was a 42–27 win-loss record, and he had a year-end ranking of sixteen.
The 2005 season started with a first round loss to Rafael Nadal at Qatar ExxonMobil Open. At the Australian Open, Youzhny was seeded 15th but lost in a five-setter in the second round to Nadal. Nadal saved a match point in the fourth set. At the Dubai Tennis Championships, Youzhny reached the quarterfinals and lost to world No. 1 Roger Federer. Youzhny lost in either the first or second round in six tournaments in a row, including the French Open, where he lost to Jürgen Melzer in three sets. At Wimbledon, Youzhny, reached the fourth round for the first time since 2002, losing to Fernando González in three sets. In July, at both the Swedish Open and the Generali Open, Youzhny reached the quarterfinals, losing to Tommy Robredo and Gastón Gaudio respectively. At the Western & Southern Financial Group Masters in Cincinnati, Youzhny reached his only ATP Masters 1000 quarterfinals of the season, but lost to 5th ranked Andy Roddick in three sets. After wins against Florian Mayer and Jonas Björkman at the 2005 US Open Youzhny lost in round three to Xavier Malisse, after leading 2–0 in sets. After a third round loss to Guillermo Coria at the China Open, Youzhny reached the quarterfinals of the Kremlin Cup where he was upset by wild card entry Dmitry Tursunov. In his last tournament of the season, Youzhny lost his title at the St. Petersburg Open, losing to Robin Vik in the quarterfinals. Youzhny ended the season with a 23–23 win-loss record, making it one of his worst seasons in his career, and ended the year as world No. 43.
January 2006 started with victories against Jonas Björkman and Davide Sanguinetti, but a quarterfinal loss to Tommy Haas at the Qatar Open This was followed by a first round defeat by Xavier Malisse at the Australian Open. However, Youzhny steadily improved by reaching the quarterfinals of the PBS Zabreb Indoors and then the semi
Mikhail Youzhny