Antimicrobial exposure contributes to the emergence and spread of multidrug-resistant organisms. As rates of colonization and infection with these organisms are among the highest in the population of chronic hemodialysis patients and antimicrobial exposure among this patient population is extensive, it is imperative to prescribe antimicrobials judiciously. Thirty to forty percent of chronic hemodialysis patients receive at least one dose of antimicrobials in outpatient centers over a one-year period. Up to 30% of these antimicrobials are prescribed inappropriately, as per national guidelines. The predominant reasons include (i) failure to de-escalate to a more narrow-spectrum antimicrobial, (ii) criteria for infection, especially skin and soft tissue infections, are not met, and (iii) indications and duration for surgical prophylaxis for minor vascular-access-related procedures do not follow recommended guidelines. Vancomycin, third- or fourth-generation cephalosporins and cefazolin are the most common antimicrobials or antimicrobial classes prescribed inappropriately. Antimicrobial stewardship programs reduce both inappropriate antimicrobial exposure and associated costs. Effective strategies include (i) education, (ii) guidelines and clinical pathways, (iii) antimicrobial order forms, (iv) de-escalation therapy, and (v) prospective audit and feedback. Dialysis centers need to identify a team of individuals that will lead the antimicrobial stewardship program. Administrative and financial support for this team is essential. After implementation of the program, regular monitoring for compliance with strategies, and identifying factors that are preventing compliance are necessary. The efficacy of the program should also be evaluated at regular intervals through process and outcome measures.