Many current antiretroviral combinations used to manage HIV disease are frequently associated with long-term toxicity and tolerance problems that potentially jeopardise their ongoing success. While some patients may need to initiate antiretroviral therapy with complex regimens, simplified and less toxic regimens are thought to be necessary for ongoing virological and clinical benefit of antiretroviral therapy in the vast majority of patients. This review summarises published studies of simplification of antiretroviral regimens, so-called "induction-maintenance" strategies. While virological suppression is maintained in the vast majority of patients undertaking these strategies, this may not be true for patients who began treatment with suboptimal antiretroviral regimens. Switching away from protease inhibitor therapy has been associated with improvements in metabolic abnormalities but has not been shown to improve body habitus changes induced by these agents. In contrast, strategies involving a switch from thymidine analogue therapy have been associated with improvements in body habitus. Induction-maintenance strategies have also been associated with improved tolerability of antiretroviral therapy. While current evidence suggests that these strategies are generally virologically safe and associated with improved tolerability, further studies are required to establish whether long-term toxicity is prevented or adherence is improved.