The risks and benefits of stopping antiretroviral therapy in patients admitted to the ICU are largely unmeasured. In many cases therapy has to be stopped, as parenteral preparations are unavailable for all but one of the antiretroviral agents. Stopping treatment suddenly may be associated with increased risk of resistance because of the long half-life of some of the drugs, and also the risk of increased immunosuppression due to the viral load rebounding. Drugs given through the enteral route may be poorly absorbed, which again may lead to drug resistance. By inhibiting cytochrome P450 3A4 the drugs interfere with the metabolism of many other compounds routinely used in the ICU. Furthermore, the drugs themselves are occasionally associated with severe toxicity such as pancreatitis and lactic acidosis, which can have devastating consequences. Much active research in all of these areas is now needed.