Vascular prosthesis infections are potentially severe adverse events following vascular reconstruction. They are often associated with a high morbidity and mortality, especially in the aortofemoral region. The present article outlines the diagnosis, prevention and treatment of vascular graft infections in a clinical setting. The clinical presentation, inflammatory markers, microbiological work-up and imaging studies can contribute to diagnosing a prosthesis infection. Regarding the bacterial spectrum involved in the etiology of prosthesis infections, single organism infections (monoinfections) have become less significant over the past years, whereas infections with multiple organisms now constitute the most abundant microbiological constellation. Also, infections with resistant bacterial strains have been increasing in number over the past years and deserve special consideration. It remains unclear whether both aspects are due to a true epidemiological change or are the result of advanced molecular microbiological diagnostic methods. While during the past decades perioperative antibiotic prophylaxis was regarded as the most important measure for preventing prosthesis infections in vascular surgery, other primary preventive hygiene strategies have been increasingly explored and grouped together in the sense of preventive bundles. In most cases of deep postoperative infections involving a prosthetic device in the aortofemoral region, explantation of the prosthesis will be required. In situ and extra-anatomical reconstructions are often performed in such cases and the decision process to develop an optimal treatment plan must consider several individual factors. In select patients, palliative preservation of the prosthesis despite surrounding infection (i.e. graft salvage) and best conservative management in combination with local surgical measures, such as incision and drainage and vacuum therapy, deserve consideration as a treatment option for patients with a high surgical risk.