Infections caused by vancomycin-resistant enterococci (VRE) may be difficult to treat because of the limited armamentarium of antimicrobial agents. The difficulty is compounded in pediatric patients in general and neonates in particular because many of the newer antimicrobials have not been studied or approved for children. We report a 3-week-old infant who developed enterococcal bacteremia on post-operative day 10 after a surgical palliation for complex congenital heart disease that was complicated by acute renal failure. Despite removal of vascular catheters and antimicrobial regimens that included linezolid, quinupristin/dalfopristin, ampicillin/sulbactam, rifampin, and gentamicin, bacteremia persisted. It was not cleared until daptomycin (in combination with doxycycline) was started. This is the first case of successful treatment of probable endocarditis due to VRE in a neonate using a daptomycin-containing regimen.