Improving treatment adherence in patients with diabetes remains an important objective of behavioral science research. However, progress is often limited by the heterogeneity in methods used to measure treatment adherence and difficulties in generalizing across methodologies. Various measurement methods are often used with little attention paid to questions regarding validity. Doubts about validity of adherence measurement often lead investigators to measure distal clinical outcomes instead, such as glycemic control, resulting in a loss of information. This article provides an overview of the literature on diabetes medication adherence, with a focus on measurement issues. We also consider work conducted in other chronic illnesses, particularly HIV/AIDS, that may have value in guiding future directions of diabetes medication adherence research. We highlight the need for focused investigation on how characteristics of self-report methodologies affect the validity of patient responses and conclude with practical recommendations based on the current state of the science.