There are frequent side effects of antiviral therapy, often of minor magnitude, but sometimes incompatible with the continuation of therapy or life threatening. The most common adverse effects are influenza-like symptoms, occurring in more than half of the patients, especially during the first treatment period, and psychiatric symptoms (depression, anxiety, irritability, insomnia), which occur around the third month of treatment from 12 to 41% of patients. However, in persons with chronic hepatitis C, a high lifetime prevalence of major depressive disorder and panic disorder, and brief recurrent depression have been observed, irrespective of PEG-INF treatment and the use of alcohol and narcotic drugs; such associations between mood and anxiety disorders and chronic hepatitis C may reflect a high prevalence of bipolar disorder, which is more difficult to diagnose using non-dedicated screening tools. Some symptoms before treatment start, such as lack of pleasure or interest, asthenia, loss of appetite, social withdrawal, reduced work function, and hostility, are highly predictive of the onset of depressive disorders during antiviral therapy. Poor cognitive performance prior to antiviral therapy, coupled with the only depressive symptom of sadness, is predictive of more severe depressive disorders during antiviral treatment. However, cognitive deficits found before therapy appear potentially reversible and tend to completely recede when there is a virological response sustained by antiviral therapy. The presence of severe psychopathological symptoms leads to a reduction in posology and high rates of discontinuation of antiviral therapy.