In the era of oral pharmacotherapy for erectile dysfunction, penile prosthesis implantation continues to provide a reliable and effective treatment modality with a high satisfaction rate, although it is now regarded as a last line of therapy. The most troublesome complication of prostheses is infection that may result in further multiple surgeries, loss of penile tissue, economic losses, and frustration for both patients and physicians. Adopting a high standard of sterile techniques, administering prophylactic antibiotics, following careful surgical procedures, and choosing devices with an antibiotic coating should significantly decrease the occurrence of infection. When facing infection of a penile prosthesis, early identification and prompt removal of all foreign bodies should produce favorable results. However, reimplantation in infected cases is a difficult task due to scar formation in the corporal bodies and shortening of the penis. Another promising choice is a salvage procedure with aggressive lavage and immediate or delayed (within 72 hours) replacement with a new device. The advantages of the salvage procedure are that most of the length of the penis can be maintained and it has a success rate exceeding 80%.