Lopinavir/ritonavir approval for use in antiretroviral treatment 10 years ago was very important for the recognition of boosted protease inhibitor (PI)-based therapy as an attractive option for first-line therapy. Being coformulated with ritonavir and having less toxicity than former PIs it allowed for effective and durable virologic suppression with less impact on quality of life. It soon became the standard of care for salvage therapy in its class. Since then, however, its central role has been challenged by new PIs with a more favorable impact on lipid profile, better gastrointestinal tolerability or that are more active in the setting of multidrug resistance. This article summarizes the main clinical studies with lopinavir and discusses its particular characteristics as well as its possible current role in antiretroviral therapy.