Studies that utilize radio frequency plasma modification as a strategy to tune the surface properties of polymeric constructs with the goal of enhancing their use as biomedical devices have grown considerably in number over the past decade. In this Review, we present the importance of plasma surface treatment to biomedical applications, including tissue engineering and wound healing. First, we introduce several key polymeric materials of interest for use as biomaterials, including those that are naturally derived and synthetic. We, then, provide an overview of possible outcomes of plasma modification, such as surface activation, etching, and deposition of a thin film, all of which can be used to alter the surface properties of a given polymer. Following this discussion, we review the methods used to characterize plasma-treated polymer surface properties, as well as the techniques used to evaluate their interactions with biological species of interest such as mammalian cells, bacteria, and blood components. To close, we provide a perspective on future outlooks of this exciting and rapidly evolving field.