Kaposi sarcoma (KS) is an angioproliferative tumor with infectious etiology, driven by viral infection of endothelial cells (EC) by Kaposi sarcoma herpesvirus (KSHV/HHV8). KS is the most common AIDS-associated malignancy, resulting in significant morbidity and mortality in the absence of immune-reconstitution. While KS incidence has decreased substantially in the post-HAART era, there is an ongoing need for affordable and effective therapies that specifically target KS/KSHV, particularly in resource-limited areas where KS is endemic and KSHV/HIV co-infection rates are high. In my dissertation, I aim to provide an in-depth review of the research to date on KSHV with a focus on how host genes, such as HO-1, can modulate KSHV infection and tumorigenesis.