Remarkable progress has been made in the management of HIV/AIDS since the first cases of AIDS were reported in the US in 1981. By 1983 HIV was identified as the cause of AIDS and the first antiretroviral, AZT, was approved in 1987. Unfortunately it soon became apparent that AZT monotherapy resulted in incomplete viral suppression and the rapid emergence of antiretroviral drug mutations resulting in a time-limited clinical benefit of the drug. Highly active antiretroviral therapy (HAART), which typically comprised of three drugs including a protease inhibitor or non-nucleoside reverse transcriptase inhibitor, was introduced in 1996 together with HIV viral load quantitation for prognostication and routine monitoring of patients. These advances were followed by an almost immediate rapid decline in HIV related morbidity and death. However these early “HAART” regimens were also associated with very high pill burden and newly emerging drug toxicities such as lipoatrophy and metabolic syndrome which were initially poorly understood. Specific drug toxicities have now been well characterised and most of the first generation nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) have been replaced by a second generation of drugs which are much better tolerated and have few short or long term toxicities. A number of these newer drugs have been co-formulated to reduce the pill burden and increase patient convenience. New generations of nonnucleoside reverse transcriptase (NNRTI) and protease inhibitors and new classes of drugs such as integrase and entry inhibitors emerging over the last five years have provided effective and safe ART options for heavily treatment experienced patients.. As a result it is expected in contemporary practice that most ART treatment naive and experienced patients will achieve a persistently undetectable plasma HIV viral load of < 40 copies/ml and improvement or maintenance of immune function. The major ongoing challenges in HIV management include: 1) maintaining durable adherence, 2) avoidance of drug toxicities and interactions and 3) prevention, recognition and management of non-AIDS conditions such as vascular disease, liver disease or malignancy.