Heart valve replacement is the most common cardiac surgical operation performed worldwide for infective endocarditis (IE). Long-term durability and avoidance of infection relapse are the goals of the procedure. However, no detailed guidelines on prosthesis selection and surgical strategies are available, which should be guided by a comprehensive evaluation of the extent of the infection and its microbiological characteristics, the clinical profile of the patient and the risk of infection recurrence. Conventional mechanical or stented xenografts are the preferred choice for localized heart infection. In cases of complex IE with involvement of the root or the aorto-mitral continuity, the use of homograft is suggested according to the surgeon's and center's experience. The use of homograft needs to be balanced against the risk of structural degeneration. Prosthetic bioroot and prosthetic valved conduit with a mechanical or bioprosthetic valve are also considered acceptable alternatives in patients with aortic valve endocarditis. The further development of preservation techniques to enable the longer durability of allogeneic substitutes is required. We discuss current evidence for the use of valve substitutes in heart valve endocarditis and propose an evidence-based algorithm for the choice of treatment.