Infection following Mechanical Circulatory Support (MCS) has been associated with significant morbidity and mortality. Despite improvements in technology infection is still considered a relatively common complication; 59% of patients are free of a major infection at 12 months. In 2004, there had been a replacement of pulsatile to continuous flow ventricular assist device (VAD) systems with significant decrease in infection incidence. Following MCS placement, occurrence of VAD-specific or VAD-related infection, has not affected bridge to transplant survival, but may have contributed to infection before transplantation. There is lack of comparative studies in infection prevention strategies in MCS recipients, and best practices literature is not available. In 2017, the International Society of Heart and Lung Transplantation (ISHLT) in collaboration with ICCAC, published a consensus document of prevention and management strategies for MCS recipients. MCS use has increased in the pediatric population for heart failure primarily as a bridge to transplantation with overall infection rates of 17–69% with reduced rates in recent studies. The fifth annual Pediatric Interagency Registry for Mechanical Circulatory Support (PEDIMACS) in 2021, included 1011 <19 years of age that had a VAD between September 2012 and December 2020; 12% developed an infection within 2 weeks and 20% >2 weeks after VAD implantation. Although fungal infections are not common (6–23%) compared to bacterial infections, they have been associated with high morbidity and high mortality (65–71%). Candida species is the most common pathogen. Risk factors for fungal infections in VAD recipients remain incompletely understood. According to the ISHLT 2017 consensus, routine antifungal prophylaxis is not necessary.