Kaposi sarcoma herpesvirus (KSHV) is the infectious etiological agent of several malignancies, lymphoproliferative disorders, and immune-dysfunction syndromes with significant morbidity and mortality in HIV-infected and immune-compromised individuals. While incidences of AIDS-associated malignancies caused by KSHV have declined considerably since the implementation of highly active antiretroviral therapies (ART), those individuals who develop KSHV-associated diseases have few, and often ineffective, treatment options. This underscores the continued need for research to understand KSHV pathology and development of new therapies.