From ship hulls to bandages, biological fouling is a ubiquitous problem that impacts a wide range of industries and requires complex engineered solutions. Eliciting materials to have antibacterial or antifouling properties describes two main approaches to delay biofouling by killing or repelling bacteria, respectively. In this review article, we discuss how electrospun nanofiber mats are blank canvases that can be tailored to have controlled interactions with biologics, which would improve the design of intelligent conformal coatings or freestanding meshes that deliver targeted antimicrobials or cause bacteria to slip off surfaces. Firstly, we will briefly discuss the established and emerging technologies for addressing biofouling through antibacterial and antifouling surface engineering, and then highlight the recent advances in incorporating these strategies into electrospun nanofibers. These strategies highlight the potential for engineering electrospun nanofibers to solicit specific microbial responses for human health and environmental applications.