Anti-tumor necrosis factor (TNF) agents have radically changed the treatment of inflammatory bowel diseases. Although a significant amount of patients respond to therapy, others experience only a partial response or do not benefit at all. Although, in some cases, the mechanistic action of the anti-TNF therapy may explain such findings, we have now learned that many patients may instead suffer from inadequate dosing and drug exposure. Such heterogeneity in how patients respond to therapy may be explained by multiple pharmacodynamic variables, such as factors that alter drug clearance, including the level of systemic inflammation, the presence of antidrug antibodies, and concomitant use of immunomodulators. Multiple studies have found that low-serum anti-TNF levels are associated with active disease and that adjusting the dose in these cases may offer a therapeutic benefit. In this review, we discuss the most recent evidence on therapeutic drug monitoring in patients with inflammatory bowel disease receiving anti-TNF biological therapies.