In recent years the availability of highly active antiretroviral therapies and prophylaxis and treatment of opportunistic infections in patients with HIV-disease have reduced morbidity and mortality. Many different drugs may be prescribed in a patient simultaneously. Therefore, the potential for interactions between different substances is increased. The possible mechanisms of drug interaction concern pharmakokinetics (absorption, metabolism, elimination) and pharmakodynamics. They can lead to significant changes in plasma concentrations and may affect efficacy and toxicity of a drug. One of the most important mechanisms of interaction is the inhibition or induction of the hepatic cytochrome P-450 enzyme system. All protease-inhibitors are metabolized by CYP450, mostly by the subunit 3A4. Proteinase-inhibitors are themselves very potent inhibitors of CYP4503A4 and increase the concentration of drugs metabolized this way. This article summarises the most important mechanisms of drug interactions and demonstrates the most frequent and clinical significant consequences.