Boceprevir and telaprevir are inhibitors and substrates of the cytochrome P450 3A4 family. With the use of these HCV protease inhibitors as part of standard therapy for chronic hepatitis C genotype 1 infection, drug-drug interactions with multiple medications being inductors, inhibitors, or substrates of cytochrome P450 3A4 can be expected. Due to the complexity of these interactions, predicting the expected magnitude and sometimes even the direction of the effect has proven to be difficult. Pharmacokinetic studies should be carried out to evaluate drugs with clinical relevance and possible interactions. This review focuses on the data available regarding drugs that are frequently used in the setting of addiction or used by patients with addiction. In addition to highlighting relevant drug-drug interactions, alternative drugs that can be safely used are suggested.