Infections deriving from medical devices represent a critical problem in health care causing suffering for patients, prolonged medical care, as well as consuming both human and monetary resources. An attractive solution is physical or chemical surface modifications of devices rendering them antibacterial and/or antifouling. However, the testing of such surfaces and coatings faces a range of challenges where one important is the predictability of in vitro assays for the outcome in vivo and in clinic. In this short review, we discuss what we consider is a major obstacle for design and evaluation of antimicrobial surfaces: microbial interspecies interactions. We give examples from the urinary tract, airways and from the oral cavity of functional consequences of such interactions in microbial communities, their therapeutic application for treatment, and how multi-species biofilms may influence the successful outcome of antimicrobial or antifouling surfaces. Furthermore, we suggest a path forward for in vitro testing taking these complexities into account during research and development.