Infections continue to be a major cause of morbidity and mortality in patients with end-stage renal disease. While rates of all-cause hospitalization of prevalent end-stage renal disease patients receiving hemodialysis reported by the United States Renal Data System fell from 1993 to 2007, rates of hospitalization for infections rose by 26%. Developing a better understanding of the reasons for this rise and employing strategies to reverse it have become a priority for patients, providers and regulatory agencies in the USA. In addition, recent episodes of transmission of bloodborne hepatitis viruses in outpatient healthcare facilities, including hemodialysis centers, related to suboptimal infection control and injection safety practices, have raised concerns about patient safety. In this article, we review many of the current infection control challenges facing outpatient dialysis centers and discuss recommended infection control policies and practices aimed at combating these challenges.