Nosiheptide is a bicyclic thiopeptide antibiotic produced by several species of actinomycetes, notably Streptomyces, first reported by Japanese researchers in 1970. Unlike other bicyclic thiopeptides such as thiostrepton, the second macrocyclic ring is linked by relatively fragile lactone and thiolactone bridges to the core cyclic peptide. Nosiheptide has broad spectrum antibacterial activity, and has recently demonstrated a prolonged post-antibiotic effect in both nosocomial and community-acquired MRSA compared with vancomycin. Despite its long history in animal health, nosiheptide has not been extensively studied and is regarded as a “lost antibiotic” largely escaping intensive investigation for human application.