There is little doubt that basic biomedical research efforts in the last fifty years have provided great mechanistic insight into disease processes. While these advances are likely to take a prominent place in historic archives, they barely appear on the radar screen when compared to the history-altering impact of past and present global infectious diseases. The plague(s), malaria, yellow fever, schistosomiasis, influenza, small pox, polio, and human immunodeficiency virus (HIV) have all exacted a heavy toll on humanity and have truly altered the course of history during the past millennium. Although significant strides recently have been made to halt some of these disease-causing agents, mainly via vaccine development, therapeutic advances to treat and cure others have been painfully slow. A number of reasons may account for this slow progress toward therapeutic development, ranging from lack of significant interest by modern countries’ funding agencies, regarding parasite research, for example, to the uncanny ability of certain infectious agents to elude mechanistic scrutiny. The best recent example of this latter scenario is the multitude of difficulties associated with the biology, pathogenesis, treatment, and prevention of HIV infection. While heavy emphasis is currently directed toward HIV vaccine development, this preventive approach has a variety of hurdles to clear, including a better understanding of the basic biology of HIV infection. To underscore the complexities associated with the basic biology of HIV, only recently have years of basic research efforts begun to pay dividends and shed some light on mechanisms