The incidence and prevalence of patients treated for end-stage renal disease (ESRD) continually increases in the United States. Data from the U.S. Renal Data System (USRDS) 2006 Annual Report show that for 2004, 335 034 patients were treated for ESRD with either hemodialysis (309 269) or peritoneal dialysis (25 765), and 102 104 patients started dialysis. The total number of patients on dialysis is higher as the USRDS does not include data on non-Medicare patients. After cardiovascular disease, infections are the second most common cause of death of patients receiving long-term dialysis (12% to 22%), and a leading cause of hospitalization. Data on the mortality of patients on dialysis followed for 16 years, a longer period than in the USRDS, show that infections account for 36% of deaths versus 14.4% for cardiovascular disease. Sepsis is responsible for more than 75% of deaths caused by infection. Abnormalities of cellular immunity, neutrophil function, and complement activation are associated with chronic renal failure and cited as risk factors for the increased susceptibility to infection. Most dialysis-related infections are caused by common microorganisms rather than by opportunistic pathogens and are primarily related to vascular and peritoneal dialysis access. This chapter focuses on the treatment of infections related to dialysis access devices.