Lymphoma is a well-recognized complication in patients infected with HIV. Although its incidence has declined since the advent of antiretroviral therapy, it remains higher than in the general population. Several recent studies have noted improvement in clinical outcomes with the use of modern chemoimmunotherapy regimens. In patients who experience relapse, however, fewer data are available on the role of immunotherapy and its impact on outcomes. This case report presents 2 patients with relapsed HIV-associated lymphoma who experienced a second complete remission after treatment with the immunotherapy agent brentuximab vedotin.