Infections due to multidrug-resistant pathogens have an increasing impact on patients undergoing cardiac surgery. Preoperative infections, such as endocarditis, and postoperative infections, including wound and device infection, influence patient outcomes. Special interest needs to be taken in patients admitted to cardiac surgical intensive care units, as these patients are at high risk for infections, particularly nosocomial pneumonia, catheter-related and wound infections. The increasing numbers of infections due to Gram-positive multidrug-resistant pathogens underline the necessity for newer antibiotics with bactericidal effects and a more favorable profile of side effects. Daptomycin, a lipopeptide antimicrobial agent with bactericide activity against Gram-positive organisms, has been successfully used in the treatment of complicated infections due to Gram-positive multidrug-resistant pathogens, especially regarding endocarditis, wound infections, device and catheter-related infections in intensive care units. In this review, the authors will summarize therapeutic potential of daptomycin in cardiac surgery and postoperative intensive care.