The first quinolone compound, nalidixic acid, showed activity against a limited number of Gram-negative micro-organisms. 'One step' resistance developed in vitro and during treatment. Resistance was not mediated by transfer of R-plasmids, which is a characteristic of all quinolones. Newer quinolones like oxolinic acid, piromidic acid, cinoxacin and pipemidic acid exhibit an extended spectrum of activity against Gram-negative bacteria at lower MIC values. In recent years fluorinated quinolones were introduced like ciprofloxacin, norfloxacin, pefloxacin, ofloxacin, enoxacin and amifloxacin. These compounds exhibit in vitro a broad spectrum of activity against Gram-negative and Gram-positive bacteria at MIC values seventy to four hundred times less than those for nalidixic acid. The in vitro activity of these compounds has been investigated in a large study of uncomplicated urinary tract infections in general practice (PINISU). No resistance was found. The fluorinated quinolones are very promising antimicrobial agents for a limited number of indications.