This chapter discusses the chemistry, mechanism of action, antimicrobial activity, resistance, pharmacokinetic properties, drug interactions, toxicity and adverse effects, administration, dosage and clinical applications of peptide antibiotics. Peptide antibiotics include polymyxins, glycopeptides, bacitracin, and fosfomycin with a variety of actions against bacteria. Polymyxin B and colistin are similarly rapidly bactericidal and highly active against many species of gram-negative organisms, such as Escherichia coli, Salmonella, and Pseudomonas aeruginosa, but not against Proteus, Serratia, or Providencia. Glycopeptides antibiotics show activity against gram-positive bacteria and particularly against gram-positive cocci. Bacitracin is a polypeptide product of Bacillus subtilis. It is bactericidal to gram-positive bacteria but has little activity against gram-negative organisms. Fosfomycin has a broad spectrum of activity against a wide range of gram-positive and gram-negative bacteria. It is highly active against gram-positive pathogens such as Staphylococcus aureus and Enterococcus, and against gram-negative bacteria such as P. aeruginosa and Klebsiella pneumonia.