Drug resistance to human immunodeficiency virus (HIV) is a major factor in the failure of antiretroviral therapy.1 In order for practitioners to provide effective pharmaceutical care to their HIV patients, it is essential that they understand the mechanisms of HIV drug resistance as well as the various factors that can contribute to its emergence. This article is based on didactic content from the infectious disease section of the Integrated Sequence II Course in the PharmD program at South University. In the course, students are first given an overview that includes key structural components of HIV and a discussion of the HIV life cycle. A detailed presentation on the pharmacology of the various classes of antiretroviral agents follows. The clinical impact and prevalence of HIV drug resistance is then discussed along with factors that might contribute to it. Mechanisms of drug resistance for each class of antiretroviral agents are presented in detail followed by a discussion of the basis and clinical utility of HIV drug resistance testing. Finally, new targets for HIV pharmacotherapy are presented along with an overview of new antiretroviral agents that are being developed. Content taught in lecture is reinforced by relevant case studies that students work on in small groups during the recitation period.