Ramoplanin is a glycolipodepsipeptide antibiotic obtained from the fermentation of Actinoplanes sp. ATCC 33076 that exhibits activity against clinically important multi-drug-resistant, Gram-positive pathogens including vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate resistant Clostridium difficile. Ramoplanin was first isolated as a complex of three closely related components A1, A2, and A3. Preclinical studies have also demonstrated that ramoplanin exerts a rapid bactericidal effect on S. aureus biofilms and that a clinical vancomycin-resistant S. aureus strain containing the vanA gene was susceptible to ramoplanin. Ramoplanin blocks bacterial cell wall biosynthesis by interfering with peptidoglycan production. Ramoplanin inhibits the N-acetylglucosaminyltransferase-catalysed conversion of lipid intermediate I to lipid intermediate II, a step that occurs before the transglycosylation and transpeptidation reactions. Ramoplanin’s mechanism of action is distinct from that of glycopeptides. Unlike glycopeptides, ramoplanin does not complex with the D-Ala–D-Ala sequence of cell wall precursors. Ramoplanin is being developed for the targeted prophylaxis of recently treated patients with C. difficile infection (CDI) at high risk for infection relapse. Twelve Phase I studies, two Phase II studies (one in CDI and one in VRE) as well as one Phase III study (in VRE) have been conducted