In the early days of the HIV epidemic, Kaposi’s sarcoma (KS) was the most common HIV-presenting illness for men who have sex with men (MSM). The malignancy is caused by HHV-8 (or KSHV), a human herpes virus which can be detected in the tissues of KS lesions. After discovery of the viral etiology a number of molecular techniques were developed in attempts to identify HHV-8 and the immune response to the virus in asymptomatic individuals. It was hoped these tests would help better define the population at risk and provide tools to help to understand the pathogenesis and epidemiology of the disease. However major issues exist with the sensitivity, specificity and predictive values of these tests making comparisons between studies unreliable. Today, the diagnosis of KS is much less common. It is unclear why this malignancy is seen less frequently in MSM newly diagnosed with HIV. Although highly active antiretroviral therapy (HAART) either directly or indirectly has had a major impact, this may not be the entire explanation. Other considerations include changes in sexual practices, and the impact of HAART on cofactors that mediate HHV-8 related disease. If HAART is the major driver, it remains unclear whether it is a consequence of a decrease in HHV-8 prevalence or viral load, whether there has been an impact on transmission, or whether HAART has altered viral expression into clinical disease. In this paper we will discuss the various hypotheses, and will review the molecular tests available to test for HHV-8 and whether or not they can be used in a current cohort to better determine what has happened to HHV-8 and KS.