Efavirenz (Sustiva), Bristol-Myers Squibb) is a non-nucleoside reverse transcriptase inhibitor that has been used successfully since the late 1990s to treat HIV-1 infection, and has since become a cornerstone of antiretroviral therapy. The efficacy and potency of efavirenz has been established in many clinical trials and cohort studies, where it has been compared with unboosted or ritonavir (Norvir, Abbott Laboratories Ltd)-boosted protease inhibitors, nevirapine (Viramune, Boehringer Ingelheim Ltd); and three nucleoside analog-based regimens. Pharmacokinetics allowing for a convenient once-daily administration make efavirenz one of the first agents to be included in once-daily regimens. Tolerability of efavirenz is satisfactory, although CNS-related toxicity can occur, and is still poorly understood. New insights into the pharmacokinetics of efavirenz could help to manage this unwanted toxicity. This drug profile will examine the principal data concerning the efficacy, pharmacokinetics and safety that have made efavirenz a standard of care in HIV-1 therapy, and will comment on new data that could change the way efavirenz is used in the near future.