HIV, a major cause of morbidity and mortality worldwide has been transformed by antiretroviral (ARV) therapy into a manageable condition. Drug resistance, tolerability and drug interactions remain major concerns when choosing ARV therapy. Raltegravir , the first integrase inhibitor in the armamentarium against HIV, has been shown to be efficacious in both treatment-naïve and treatment-experienced patients when used in combination as part of nucleoside-reverse transcriptase inhibitor-containing regimens. Its key advantages include safety, tolerability and fewer drug interactions but it has some important limitations such as a lower barrier to resistance and a twice-daily dosing schedule. Its role in nucleoside-sparing regimens is under investigation.