This exploratory study examines the contextual factors that lead to episodic nonadherence to highly active antiretroviral therapy. Unlike global adherence that refers to the overall probability that a participant will take his or her medication over a given time period, episodic adherence refers to whether an individual took a particular dose (e.g., Saturday morning, 17 September). Semi-structured, qualitative interviews were conducted with a convenience sample of 27 consecutive participants enrolled in ongoing adherence trials who had missed at least one dose of antiretroviral medication during the past 2 days. A qualitative analysis revealed that routinization of pill regimens and factors associated with the participant's ability to maintain these routines (e.g., time of day of scheduled dose; location of participant at time of dose) play an important role in successful adherence. In addition, psychosocial factors such as psychological distress, substance abuse, and active and unpredictable social lives may act as barriers to adherence. Implications for adherence interventions are discussed.