Outpatient parenteral antimicrobial therapy (OPAT) is an effective strategy for managing infections that require prolonged intravenous (IV) therapy, while reducing hospital length of stay and healthcare costs. Successful OPAT implementation requires careful patient selection, a structured multidisciplinary team, and individualized models of care tailored to both infection complexity and patient-specific factors. We provide a narrative overview of OPAT management, integrating current guideline recommendations and evidence from the literature. OPAT represents a valid model of care for patients requiring prolonged IV antimicrobial therapy, enabling a safe transition from inpatient to outpatient settings without compromising clinical outcomes. Moreover, it delivers substantial organizational and economic benefits, with marked reductions in hospital bed stays and associated costs. OPAT is a safe and effective alternative to prolonged hospitalization, especially for complex infections caused by pathogens with limited therapeutic options.