Lopinavir is a new protease inhibitor that is structurally related to ritonavir. It recently was approved by the Food and Drug Administration as a coformulation with ritonavir under the brand name Kaletra. Ritonavir substantially increases lopinavir drug exposure by inhibiting cytochrome P450 isoenzyme 3A4. Based on limited data, lopinavir-ritonavir demonstrates safety and efficacy in both antiretroviral-naive and protease inhibitor-experienced patients. It has the ability to durably suppress human immunodeficiency virus (HIV) RNA for up to 2 years in antiretroviral-naïve patients. Compared with nelfinavir, it had superior virologic control at 48 weeks in antiretroviral-naïve patients. Its side effects include diarrhea, abnormal stools, abdominal pain, nausea, vomiting, and asthenia. A number of patients experienced grade 3-4 laboratory abnormalities in liver function tests, cholesterol, and triglycerides while receiving this drug combination. The exact resistance patterns of lopinavir-ritonavir are unknown, but the Department of Health and Human Services strongly recommends it for the initial treatment of HIV-infected adults and adolescents.