Over the past decade, a causal relationship between infection with human immunodeficiency virus (HIV) and osteonecrosis has been proposed. This case report (the first example presented in the English orthopaedic literature) of multifocal (> 3 sites) osteonecrosis in a patient with HIV infection highlights the current scientific knowledge regarding incidence, predisposing risk factors, proposed biologic mechanisms, and clinical orthopaedic management. This information may become increasingly relevant for the orthopaedic clinician as more patients with HIV infection live longer.