Interleukin-7 (IL-7) is a cytokine that plays a critical role in T cell homeostasis by promoting proliferation and survival of mature T cells and also by enhancing thymic output for the generation of new T cells. IL-7 receptor expression and signaling function is perturbed in HIV infection and could contribute to disease pathogenesis. Even though highly active anti-retroviral therapy has markedly reduced morbidity and mortality in HIV-infected persons, there remains concern that a significant proportion of treated patients may experience relatively poor CD4+ T cell recovery despite sustained viral suppression. Recent human trials and animal studies suggest that IL-7 administration may provide a powerful tool to enhance T cell reconstitution in HIV-infected persons. The role of IL-7/IL-7 receptor perturbations in HIV pathogenesis and the potential to reconstitute immunity with IL-7 administration in the setting of HIV infection are important areas of investigation.