Ritonavir-boosted lopinavir (LPV/r) is a boosted protease inhibitor (PI) combination used as an alternative agent in the management of the human immunodeficiency virus (HIV). HIV treatment consists of combinations of classes of medications with complementing mechanisms of action. Protease inhibitor-based therapy is one of the mainstays of therapy. Ritonavir-boosted lopinavir can be dosed once- or twice-daily based on previous antiretroviral therapy, patient characteristics, and concomitant medications. It is currently available as an oral solution or tablet formulation and can be given without regard to food if given as a tablet. Lopinavir is extensively metabolized via the cytochrome (CYP) P450 3A4 and 3A5 hepatic isoenzymes and ritonavir is a potent inhibitor of CYP34A. Co-administration of low-dose ritonavir leads to increased plasma concentrations of lopinavir. There is potential for numerous drug-drug interactions when additional medications are administered. Clinical trials have been reported previously demonstrating the safety and efficacy of LPV/r in children, adolescents and adults and it is readily used throughout these populations. Current clinical trials are focused on examining the efficacy and toxicity of boosted-PI monotherapy as a treatment option in previously suppressed adults.