Biomaterial-associated infections have an enormous impact in terms of morbidity of the patients and costs to national health systems. Perioperative antibiotics and aseptic procedures have not proved sufficient to eradicate the occurrence of this type of infections which often lead to devastating effects. Adjunctive strategies for preventing the establishment of infections are increasingly being centered on the development of new biomaterials with anti-infective properties. The creation of new anti-infective biomaterials can be obtained by alternative approaches oriented to achieve either bacteria-repellent surfaces or bioactive surfaces expressing self-sterilizing properties when not even able to treat pre-existing infections in the surrounding tissues. Here, we offer a short overview of the currently available in vitro methods that can be used to investigate and assess the performance of anti-infective biomaterials, with special emphasis on those whose mechanism of action is based on bacteria-repellent surfaces.