Purpose The pharmacologic properties, clinical efficacy, and safety profile of the first oral protease inhibitor approved for the treatment of chronic infection with hepatitis C virus (HCV) genotype 1 are reviewed. Summary Boceprevir, approved by the Food and Drug Administration as an adjunct to the standard regimen for HCV genotype 1 infection (peginterferon alfa and ribavirin), is available in 200-mg capsules, to be administered thrice daily at seven-to nine-hour intervals (total daily dose, 2400 mg). In two Phase III clinical trials involving a total of nearly 1500 previously untreated patients who were not sufficiently responsive to or had relapsed after standard therapy, the adjunctive use of boceprevir was associated with significantly higher rates of sustained virologic response and a shorter cumulative duration of treatment. Adverse effects occurring significantly more often in clinical trial participants receiving boceprevir relative to control groups included anemia (47% versus 20%), dysgeusia (35% versus 16%), and neutropenia (25% versus 19%); these were generally not treatment-limiting effects. Due to the potential for serious or potentially life-threatening adverse events, boceprevir use is contraindicated in patients receiving any of a wide range of drugs whose clearance is highly dependent on cytochrome P-450 (CYP) isoenzymes 3A4/5 (e.g., cisapride, lovastatin, midazolam, sildenafil); boceprevir is also contraindicated for patients receiving potent CYP3A4/5 inducers such as carbamazepine, phenytoin, and rifampin, whose concurrent use can diminish boceprevir's virologic activity. Close monitoring is critical to ensure patient adherence to triple-drug therapy and, more broadly, to reduce the risk of the development and transmission of resistant HCV strains. Conclusion Previously untreated patients with chronic HCV monoinfection, as well as patients who do not respond adequately to or relapse after standard dual therapy, may benefit from adjunctive boceprevir therapy. Careful selection and close monitoring of patients receiving boceprevir are essential to avoid drug-drug interactions, reduce adverse effects, and optimize treatment outcomes.