Antimicrobial resistance (AMR) has emerged as one of the most significant global public health threats of the twenty-first century. The inappropriate use, overuse, and misuse of antibiotics have accelerated the development of resistant microorganisms, leading to increased morbidity, mortality, healthcare costs, and treatment failures. Antibiotic Stewardship Programs (ASPs) are coordinated interventions designed to optimize antibiotic use, improve patient outcomes, reduce antimicrobial resistance, and decrease unnecessary healthcare expenditures. Healthcare institutions worldwide have increasingly adopted stewardship initiatives involving multidisciplinary teams, evidence-based prescribing practices, surveillance systems, education programs, and technological innovations. This review examines the principles, implementation strategies, clinical outcomes, challenges, and future directions of antibiotic stewardship programs in healthcare settings. Findings indicate that effective stewardship programs significantly reduce inappropriate antibiotic prescribing, lower resistance rates, improve patient safety, and enhance healthcare quality. Continued investment in stewardship infrastructure, diagnostics, surveillance, and education is essential to preserve antibiotic effectiveness for future generations.