In our perinatal HIV cohort, we have observed difficulty swallowing pills as a frequent and significant barrier to adherence to highly active antiretroviral therapy. We refer to this problem as pill aversion and define it as difficulty swallowing pills with no persistent medical or structural cause as well as the anxiety and physical symptoms associated with pill swallowing. By applying cognitive behavioral theory to behavioral patterns within our pregnant HIV-infected population, we seek to better understand the development and reinforcement of pill aversion behavior. On the basis of this theory, our experience, and the pediatric pill-swallowing literature, we propose a conceptual framework for understanding the multiple causes of pill aversion and applying therapeutic interventions to a perinatal population. In a theoretical discussion, we address the roles of classical conditioning and cognitive theory in the development and experience of pill aversion in an HIV-infected pregnant population. We propose future steps for characterizing these behaviors and testing theories and interventions.