Indinavir is one of four first-generation HIV-protease inhibitors and was the most popular amongst them in the late 1990s. It was initially licensed for use alone, given three times daily, administered away from meals and together with at least 1.5 litres of fluid per day. In clinical practice, it became common for clinicians to prescribe it with a ritonavir pharmacokinetic 'boost' to remove the food restriction, reduce the pill burden and enable a more convenient twice-daily dosing schedule. However, at a ritonavir-boosted dosing schedule of indinavir/ritonavir 800/100 mg b.i.d., the regimen proved toxic and poorly tolerable, and its use diminished as newer, better tolerated PIs became available. Recent research has suggested that ritonavir-boosted indinavir administered at lower doses, particularly indinavir/ritonavir 400/100 mg b.i.d., retains potency and is considerably less toxic. As a result, there is interest in its application in resource-constrained settings.