Widespread use and misuse of penicillin and other antibiotics have resulted in development of resistance to most antibiotics. The mechanisms by which microorganisms develop resistance to antibiotics are discussed. Topics covered include acquisition of point mutations and antibiotic resistance genes, methods of transfer of resistance genes between bacteria and the advantages of synthetic antibiotics. Contribution of subtherapeutic use of antibiotics to resistance development and the response of the governments and other regulatory agencies to address the problem are also discussed.