Staphylococcus lugdunensis is a coagulase-negative Staphylococcus capable of causing infective endocarditis on native as well as prosthetic valves and implanted cardiac devices. It causes acute disease clinically indistinguishable from that caused by Staphylococcus aureus. Bacteremic infections with S. lugdunensis have a high incidence of associated infective endocarditis. Many S. lugdunensis isolates are exquisitely sensitive to penicillin G. Endocarditis caused by S. lugdunensis frequently requires surgical intervention and has a high mortality rate. Case 1: A 48-year-old woman with mitral valve prolapse, S. lugdunensis bacteremia and mitral valve endocarditis. She underwent emergent mitral valve replacement and completed treatment with intravenous nafcillin. Case 2: A 31-year-old woman with spontaneous S. lugdunensis bacteremia and tricuspid valve endocarditis. She was successfully treated medically with 6 weeks of intravenous nafcillin. Case 3: A 44-year-old man with S. lugdunensis endocarditis on congenital bicuspid aortic valve with severe aortic insufficiency. He underwent emergent aortic valve replacement and successfully completed 6 weeks of intravenous nafcillin. Case 4: A 37-year-old woman with spontaneous S. lugdunensis bacteremia and native aortic valve endocarditis. She was successfully treated medically with 6 weeks of intravenous vancomycin. Case 5: A 57-year-old woman with hemodialysis catheter-related S. lugdunensis bacteremia and native mitral valve endocarditis. She was successfully treated medically with 6 weeks of intravenous cefazolin. Staphylococcus lugdunensis is a unique coagulase-negative Staphylococcus first identified in Lyon, France, the modern name for the Roman city of Lugdunum, ergo the organism's name. Since its identification, S. lugdunensis has been described as a “Lion among coagulase-negative staphylococci” and as “a dangerous wolf in sheep's clothing” because of the tendency of clinicians to initially discount positive blood cultures with “coagulase-negative staphylococci” as probable skin contaminants and thereby delay appropriate antimicrobial therapy. We report 5 patients with S. lugdunensis endocarditis and review the adult literature for other reported cases.