A retrospective chart review was performed for all patients (N = 31) treated by the authors with daptomycin over a 12-month period for infections of bone and joints, spine, and prostheses. Data were collected for demographic patient information, therapy duration, surgical procedures, culture site and results, side effects, and clinical outcomes. Infection types included osteomyelitis (n = 16), prosthetic joints (n = 8), laminectomy wounds without osteomyelitis (n = 6), and diskitis with bacteremia (n = 1). Twenty-four patients' infections involved methicillin-resistant Staphylococcus aureus isolates (MRSA); 5 had methicillin-sensitive S. aureus (MSSA); and 4 had methicillin-resistant Staphylococcus epidermidis (MRSE). Most received daptomycin as salvage therapy at dosages of 6 mg/kg/d; mean therapy duration was 38 days (range 14-56). Daptomycin therapy was successful in 87% (27/31) of patients, determined by culture results, and magnetic resonance imaging (MRI) and computed tomography (CT) scans. In most cases, daptomycin was effective for treatment of difficult bone and joint infections caused by MRSA in this patient population.