Advances in mechanical circulatory support devices provided the technology to develop long-term, implantable left ventricular assist devices as bridge to transplant, destination therapy, and in a lesser group of patients, as bridge to recovery. Despite the benefits from this innovative therapy, with their increased use, many complications have been encountered, one of the most common being infections. With the driveline acting as a portal to the exterior environment, an infection involving this structure is the most frequent one. Because patients with destination therapy are expected to receive circulatory support for a longer period of time, we will focus this review on the risk factors, prevention, and treatment options for driveline infections.