Human immunodeficiency virus (HIV) disease is associated with dysregulation and dysfunction involving all major lymphocyte populations, including B cells. Such perturbations occur early in the course of infection and are driven in large part by immune activation resulting from ongoing HIV replication leading to bystander effects on B cells. While most of the knowledge regarding immune cell abnormalities in HIV‐infected individuals has been gained from studies conducted on the peripheral blood, it is clear that the virus is most active and most damaging in lymphoid tissues. Here, we discuss B‐cell perturbations in HIV‐infected individuals, focusing on the skewing of B‐cell subsets that circulate in the peripheral blood and their counterparts that reside in lymphoid tissues. This review also highlights recent advances in evaluating HIV‐specific B‐cell responses both in the memory B‐cell compartment, as well as in circulating antibody‐secreting plasmablasts and the more differentiated plasma cells residing in tissues. Finally, we consider how knowledge gained by investigating B cells in HIV‐infected individuals may help inform the development of an effective antibody‐based HIV vaccine.