Antibiotic stewardship plays a pivotal role in addressing the global challenge of antimicrobial resistance by promoting the optimal use of antibiotics. This comprehensive review explores the principles, strategies, technological innovations, challenges, and future directions in antibiotic stewardship. The principles of stewardship emphasize judicious antibiotic selection, dose optimization, and duration of therapy to minimize resistance development and adverse effects. Strategies for optimizing antibiotic use include clinical guidelines, multidisciplinary teams, surveillance, and rapid diagnostics, aimed at improving patient outcomes while reducing resistance rates. Technological advancements such as artificial intelligence, telemedicine, and mobile health applications are transforming stewardship practices by enhancing diagnostic accuracy, decision-making, and access to expertise. Challenges to effective stewardship include behavioral barriers, resource constraints, and the need for robust policy frameworks. Future directions focus on integrating advanced technologies, enhancing education, strengthening policy support, improving surveillance, promoting innovation in antibiotic development, and strengthening infection prevention and control measures. Addressing these areas is essential for sustaining effective stewardship programs and combating antimicrobial resistance. By implementing evidence-based strategies and fostering collaboration across healthcare sectors, antibiotic stewardship can mitigate the threat of resistant infections and ensure the continued efficacy of antibiotics for future generations