Infection was identified early in development of mechanical circulatory support devices (MCSDs) as an important cause of morbidity and mortality. Sepsis, infection of implanted pump components, and infections of percutaneous drivelines continue to limit survival and decrease quality of life for patients with a MCSD. This review examines five questions related to whether there has been progress in preventing or managing infection complications in patients with MCSDs. Have changes in patient selection, device design, and surgical implant techniques decreased the incidence of infection? Do smaller implanted blood pumps have a lower risk for infection than larger implanted blood pumps? Will fully implanted circulatory support systems have fewer infection complications than tethered MCSDs? Can optimal design of a driveline together with improvements in surgical techniques and care of the percutaneous driveline diminish the rate and consequences of driveline infections? Have improvements in the preoperative, intraoperative, and immediate postoperative management of patients with MCSDs decreased the risk of sepsis? Although infection remains an important problem for patients with MCSDs, there is evidence that we are making progress as described in this review. It is crucial that we continue.