Over the past 10 years, the management of HIV infection has been transformed by an increased number of effective antiretrovirals (ARVs), with more convenient dosing and improved tolerability. Optimal management of HIV infection includes at least three effective ARVs; from at least two different drug classes. Current strategies and drugs can effectively control HIV and significantly reduce morbidity and mortality. However, no cure is yet possible. Appropriate use of ARVs leads to suppression of virological replication (to below the limit of detection using commercial assays to measure HIV in plasma) and an increase in CD4(+) T cells with few adverse effects. Greater than 95% adherence to drug therapy is required for effective viral suppression and immunological improvement. Monotherapy, two-drug combinations, sequential ARVs, drug "cycling", and treatment interruptions are ineffective management strategies and lead to earlier disease progression and emergence of drug resistance. Drug-drug interactions are common and caution is required when prescribing ARVs that inhibit or induce the cytochrome P450 pathway.