Depression has emerged as one of the few promising predictors of treatment adherence among medical patients. This chapter discusses the research evaluating the relationship between depression and adherence to medical regimens. It considers methodological issues in the assessment of adherence and depression. The chapter reviews the empirical studies that have examined whether depressed individuals have poorer treatment adherence. Several studies have addressed adherence in patients infected with human immunodeficiency virus (HIV). The chapter focuses on the relationship between depression and adherence and identifies key studies that address the question of whether adherence mediates the relationship between depression and health outcome. There are two predominant approaches to measuring depression: interview and self-report. Research on depression and adherence is increasing rapidly. It is important that future research on this topic be designed with greater methodological sophistication.