Efavirenz, which is likely to be licensed in the UK and throughout Europe shortly, represents a major advance in the treatment of HIV infection. It belongs to the non-nucleoside reverse transcriptase (NNRTI) class of drugs and, as such, it should only be prescribed with other potent therapies to avoid the development of resistance. However, in the pivotal head-to-head comparison of efavirenz with lamivudine and zidovudine, treatment over a 24-week period proved superior to treatment with a standard regimen containing indinavir. The results from prolonged follow-up of this study are eagerly awaited but it is clear that a combination of efavirenz with nucleoside analogues provides a potent proteinase inhibitor-sparing regimen which may have less toxicity. Additional data also indicate that the combination of a proteinase inhibitor (indinavir) with efavirenz provides an extremely potent regimen which is well tolerated and produces complete inhibition of plasma HIV viraemia over prolonged periods of follow-up. In common with many other currently available potent anti-HIV therapies, the optimum use of this drug is being determined by ongoing clinical studies but it is clear that ease of administration (once-daily), freedom from serious side-effects and potency when used in combination are likely to represent a very considerable advance in the management of HIV infection.