Many patients who have type 2 diabetes mellitus (DM) require several different medications. Although these agents can substantially reduce diabetes-related morbidity and mortality, the extent of treatment benefits may be limited by a lack of treatment adherence. Unfortunately, little information is available on treatment adherence in patients with type 2 DM. Available data indicate substantial opportunity for improving clinical outcomes through improved treatment adherence. Factors that appear to influence adherence include the patient’s comprehension of the treatment regimen and its benefits, adverse effects, medication costs, and regimen complexity, as well as the patient’s emotional well-being. Outcomes research emphasizes the importance of effective patient—provider communication in overcoming some of the barriers to adherence. This article offers specific suggestions for improving adherence in patients with type 2 DM seen in general clinical practice.