The human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), relies heavily on protein–protein interactions in almost every step of its lifecycle. Targeting these interactions, especially those between virus and host proteins, is increasingly viewed as an ideal avenue for the design and development of new therapeutics. In this tutorial review, we outline the lifecycle of HIV and describe some of the protein–protein interactions that control and regulate each step of this process, also detailing efforts to develop therapies that target these interactions.