Complications related to infectious diseases have significantly decreased due to the availability and use of a wide variety of antibiotics and antimicrobial agents. However, excessive use of antibiotics and antimicrobial agents over years has increased the number of drug resistant pathogens. Microbial multidrug resistance poses serious risks and consequently research attention has refocused on finding alternatives for antimicrobial treatment. Among the various approaches, the use of engineered nanostructures is currently the most promising strategy to overcome microbial drug resistance by improving the remedial efficiency due to their high surface-to-volume ratio and their intrinsic or chemically incorporated antibacterial activity. Graphene, a two-dimensional ultra-thin nanomaterial, possesses excellent biocompatibility, putting it in the forefront for different applications in biosensing, drug delivery, biomedical device development, diagnostics and therapeutics. Graphene-based nanostructures also hold great promise for combating microbial infections. Yet, several questions remain unanswered such as the mechanism of action with the microbial entities, the importance of size and chemical composition in the inhibition of bacterial proliferation and adhesion, cytotoxicity, and other issues when considering future clinical implementation. This review summarizes the current efforts in the formulation of graphene-based nanocomposites with antimicrobial and antibiofilm activities as new tools to tackle the current challenges in fighting against bacterial targets. Furthermore, the review describes the features of graphene–bacterial interactions, with the hope to shed light on the range of possible mode of actions, serving the goal to develop a better understanding of the antibacterial capabilities of graphene-based nanostructures.