Epidemiologic studies have estimated that more than 50% of men ages 40 to 70 have some form of erectile dysfunction. Penile prosthesis implantation remains a mainstay for treatment of erectile dysfunction unresponsive to other less-invasive methods. Improvements in penile prosthesis design have extended the long-term survival of implants. As the improved design of prostheses has led to their increased mechanical survival, other complications, such as infection, have emerged as the leading causes of implant failure. This article focuses on approaches to prevention and treatment of penile prosthesis infection. © 2011.