: Inappropriate prescription practices, patient and provider knowledge and attitudes, variable availability of diagnostic and surveillance systems, and the unrestricted use of antimicrobials in animals and plants are contributory factors to the global crisis of antimicrobial resistance (AMR). : Notwithstanding that interventions to revert AMR should be tailored to the socio-politico-economic landscape, there is a global consensus for the implementation and enhancement of antimicrobial stewardship strategies. Yet the implementation of Antimicrobial Stewardship Programs (ASPs) remains relatively limited within healthcare settings and faces complex challenges in resource-limited countries. The current review summarizes the limitations of current ASPs, translation challenges in resource-limited countries, and potential solutions. : Suboptimal ASP implementation in hospitals is multifactorial. Restriction of antimicrobial use should be informed by risk-benefit analyses, including the potential for substitute prescribing, and displacement of selection pressures. Thresholds in population use of antibiotics above which AMR increases may provide quantitative targets for ASPs. Horizontal and vertical collaborations involving policymakers and the general public are of paramount importance. While impactful prescribing changes require sustained engagement of the public and health-care professionals, we warn against over-estimating the benefits of behavioral interventions. We advocate for population-level stewardship interventions in addition to investment in structural factors that will aid ASP implementation.