Dose escalation from 5mg/kg to 10mg/kg is routinely prescribed to recapture clinical response in subsets of patients with inflammatory bowel disease who experience loss of response during maintenance therapy and is supported in the FDA label for Crohn's disease. Loss of response to infliximab maintenance therapy is a well-recognized phenomenon, and there is abundant literature suggesting that durable and efficacious infliximab therapy is dependent upon optimizing serum infliximab levels. Specifically, high serum infliximab trough levels predict clinical response, but low serum trough levels and presence of infliximab antibodies are associated with loss of response. However, serum infliximab levels are not dependent upon drug dose and pharmacokinetics alone. Concurrent immunomodulator use may reduce immunogenicity against monoclonal antibody therapies, and more recently, there has been increased recognition of the importance of patient factors as well. Specifically, variability in drug metabolism and clearance has been associated with body-mass index, sex, and severity of inflammation - as measured by C-reactive protein, serum albumin, and tumor necrosis factor alpha levels. It has been demonstrated that patients with higher serum albumin levels maintain higher infliximab concentrations, lower clearance, and longer drug half-lives than patients with lower serum albumin levels; and low serum albumin correlates with poorer clinical response. Severe colonic disease is associated with higher early fecal infliximab concentration, which is inversely associated with serum infliximab levels and response to therapy. Moreover, high serum tumor necrosis factor alpha levels prior to infliximab infusion predict poorer clinical outcomes and need for dose escalation in patients with Crohn's disease and rheumatoid arthritis.