Nelfinavir (NFV) is a protease inhibitor that has been widely used for several years for the treatment of HIV infection. This has led to extensive experience with NFV-containing regimens, in which the drug has shown prolonged viral suppression, good tolerability and a unique resistance profile. In recent years, several antiretroviral drugs with some advantages over NFV have been developed. Nevertheless, NFV has favourable characteristics that make it a suitable antiretroviral compound for many HIV-infected patients. It can be used in patients who do not tolerate ritonavir even at low doses, and it is well tolerated in pregnant women, has a low-grade interaction with methadone and may be well tolerated in hepatitis C virus-co-infected patients. In addition, its new simplified posology may contribute to improved adherence.