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Antimicrobial stewardship is the primary intervention in the battle against antimicrobial resistance, but clinicians do not always apply many key antimicrobial stewardship principles to patients with significant immune defects due to lack of data and fear of bad outcomes. We review evidence regarding the application of stewardship principles to immunocompromised patients, with a focus on solid organ and hematopoietic stem cell transplant recipients.Antimicrobial stewardship programs (ASPs), targeting immunocompromised patient populations such as oncology and transplant, are gaining traction. Emerging literature suggests that several stewardship interventions can be adapted to immunocompromised hosts and improve antimicrobial utilization, but data supporting improved outcomes is very limited.The application of antimicrobial stewardship principles to immunocompromised patients is feasible, necessary, and urgent. As antimicrobial stewardship programs gain momentum across a diverse range of healthcare settings more immunocompromised patients will fall under their purview. It is imperative that centers applying antimicrobial stewardship principles share their experience and establish collaborative research efforts to advance our knowledge base in applying antimicrobial stewardship initiatives to immunocompromised host populations, both in terms of programmatic success and patient outcomes.