Ventricular assist devices improve hemodynamics in patients with heart failure, but like most implantable medical devices, they are prone to infection; organisms that are adept at forming biofilm cause most of these. Biofilm confers many advantages to the organisms, including protecting them against natural host defenses and antimicrobial therapies. This review will focus on the mechanisms of biofilm formation, including quorum sensing and subsequent changes in microbial gene and protein expression. Novel therapies targeting these processes, as well as improvements in device design and clinical management, have begun to emerge and will aid in the management of these recalcitrant infections.