Intravenous antibiotic therapy remains necessary for many patients with prosthetic joint infections. Intravenous therapies may be used for short durations before switching to oral regimens or may be used for the entirety of therapy. Factors to consider intravenous antibiotic selection include pathogen factors such as resistance profiles, host factors such as allergies, and drug factors including how difficult the selected agent would be to administer in the outpatient setting. Monitoring of prolonged intravenous therapy in the outpatient setting requires weekly monitoring of labs with specific labs required to monitor certain antibiotics. This narrative review assesses the appropriate duration, antimicrobial selection by pathogen, and monitoring parameters for intravenous antibiotic treatment of prosthetic joint infections. (Journal of Surgical Orthopaedic Advances 30(4):243-248, 2021).