Kaposi's sarcoma (KS) is the most common malignancy associated with the acquired immunodeficiency syndrome (AIDS). Recent years have witnessed a decline in the overall incidence of AIDS-related KS, as well as a greater understanding of the pathogenesis of this disease. Despite these occurrences, AIDS-related KS remains an incurable disease that can create many psychosocial problems for patients and can adversely affect their quality of life. Clinical management of AIDS-related KS has proven to be challenging. Traditional treatment approaches for both local and visceral lesions have been palliative in intent. Clinical studies have shown alitretinoin gel (Panretin) to be a useful alternative or adjunct to other treatments for the management of cutaneous KS lesions. Other therapies, such as antiangiogenesis compounds and cytokine inhibitors, are under investigation in clinical trials, and pathogenesis-directed therapies, such as anti-human herpesvirus type 8 agents, show promise for the effective control of this disease. This review highlights the epidemiology and pathogenesis of AIDS-related KS, and describes various local and systemic therapies, with a focus on new and emerging treatments.