Hemi-synthetic derivatives of glycopeptides have demonstrated bactericidal activity towards Gram-positive bacteria, including vancomycin-resistant strains (oritavancin and telavancin), and a prolonged half-life, allowing for once-daily (oritavancin and telavancin) or once-weekly (dalbavancin) administration. These compounds have proved effective for the treatment of infections caused by multidrug-resistant Gram-positive bacteria, including complicated skin and skin structure infections (oritavancin, telavancin and dalbavancin), bacteremia (oritavancin and dalbavancin) and nosocomial pneumonia. This review compares the antibacterial activity and clinical activity of three glycopeptides, oritavancin, telavancin and dalbavancin, and the natural lipoglycopeptide, ramoplanin, which, being unstable in the bloodstream, is administered orally to treat Clostridium difficile colitis and for digestive tract decontamination. All of these compounds, with the exception of oritavancin, have received Fast Track designation from the FDA because of their clinical efficacy.