One of the best kept secrets in medicine is the problem of infections in patients with end-stage renal disease. The prescription of chronic hemodialysis has not reduced the problem of infection; it has only changed the paradigm. Dialysis superimposes myriad new problems onto patients with relentless deterioration from underlying multisystem disease and poor wound healing. All end-stage renal disease and transplant programs require the input from an individual with the specialized knowledge of laboratory diagnosis, pharmacokinetics of antibiotics, antibiotic choice, antimicrobial resistance, infection control, and infection prevention. This article gives an overview of some of the complexities of infectious problems experienced by this unique biological model.