Quinolone antibacterial agents are among the most attractive drugs in the field of anti-infective chemotherapy. Quinolones target the essential bacterial type II topoisomerases, which are involved in DNA replication and metabolism. Despite a large number of quinolones approved for the treatment of bacterial infections, there have been progressive efforts for the discovery of new quinolones to overcome the problem of growing bacterial resistance. This book discusses the structural requirements of quinolones for anti-MRSA activity and introduce the newly developed quinolones to manage MRSA infections, their in-vitro effectiveness based on recent studies and structure-activity relationships.