A thorough understanding of the antimicrobial mechanisms of graphene materials (GMs) is critical to the manipulation of highly efficient antimicrobial nanomaterials for future biomedical applications. Here we review the most recent studies of GM-mediated antimicrobial properties. This review covers the physicochemical properties of GMs, experimental surroundings, and selected microorganisms as well as the interaction between GMs and selected microorganisms to explore controversial antimicrobial activities. Finally, we rationally analyze the strengths and weaknesses of the proposed mechanisms and provide new insights into the remaining challenges and perspectives for future studies.