Darunavir is currently the most recently approved HIV-1 protease inhibitor. It is approved for twice-daily dosing with ritonavir in treatment-experienced patients as young as 6 years of age and is available in numerous pill strengths. Emergence of darunavir-specific mutations is generally slow; therefore it can retain activity against viral strains that are resistant to other protease inhibitors, including tipranavir. Darunavir pharmacokinetics, clinical efficacy, resistance mutations and pharmacodynamics, and adverse effects are reviewed here. Substantial data support its use as a potent, well-tolerated option for salvage therapy in highly treatment-experienced children and adolescents.