This article compares vancomycin, teicoplanin, quinupristin-dalfopristin, linezolid, daptomycin, tigecyline, dalbavancin, telavancin, ceftobiprole, oritavancin, and ramoplanin for the treatment of complicated skin and skin structure infections (cSSSI), methicillin-resistant Staphylococcus aureus (MRSA), enterococcus, and vancomycin-resistant enterococcus. Vancomycin, a glycopeptide antibiotic, is administered intravenously, and is the mainstay of treatment for MRSA and cSSSI. While not available in the U.S., teicoplanin, another glycopeptide antibiotic, can be administered intramuscularly and has simpler dosing and monitoring requirements than vancomycin. Quinupristin/dalfopristin treats vancomycin-resistant Enterococcus faecium (VREF) infections but inhibits cytochrome P450 A3P4, and has only modest activity against MRSA pneumonia. Daptomycin effectively treats cSSSI but not pneumonia caused by MRSA, and is effective against all strains of Staphylococcus. Linezolid, available orally and intravenously, is approved to treat community-acquired and nosocomial pneumonia, cSSSI, and infections caused by MRSA and vancomycin-resistant enterococci including infections with concurrent bacteraemia and VREE Tigecycline, a glycylcycline derived from minocycline, has been approved by the FDA to treat cSSSI and complicated intraabdominal infections, and might be effective against Acinetobacter baumannii; its primary side effect is digestive upset. Dalbavancin, effective against MRSA and administered intravenously once weekly, possesses coverage similar to vancomycin. Telavancin deploys multiple mechanisms of action and is effective against MRSA and Gram-positive bacteria resistant to vancomycin. Ceftobiprole, a cephalosporin effective against MRSA, has few side effects. Oritavancin demonstrates similar activity to vancomycin but possesses extended activity against vancomycin-resistant Staphylococcus and enterococci. Ramoplanin, a macrocyclic depsipeptide, is unstable in the bloodstream but can be taken orally to treat Clostridium difficile colitis.