The pharmacotherapeutic development of quinolones was produced in the last three decades. In 1965, the first commercial product was nalidixic acid (first-generation quinolone) an then, chemists have been able to synthesize several thousands of quinolone molecules's derivatives modifying primarily at the N-1 position and at the C-6, C-7 and C-8 positions. The structural changes incorporated into these new compounds enhanced pharmacodynamic characteristics and pharmacokinetic profiles. Third-generation quinolones (levofloxacin, clinafloxacin, sparfloxacin, grepafloxacin, DU-6859a and trovafloxacin) have several advantages over first-generation quinolones (nalicixic acid, cinoxacin and oxolinic acid) and second-generation quinolones (norfloxacin, enoxacin, ciprofloxacin, pefloxacin, ofloxacin, lomefloxacin and fleroxacin). The new fluroquinolones are well absorbed in the duodenum and jejunum. They have large volumes of distribution and their penetration into different tissues and body fluids in humans has been demonstrated, reaching concentrations equal to or greater than those observed in plasma. The third-generation quinolones are broad-spectrum antimicrobials with an improved in vitro potency against gram-positive and gram-negative bacteria, including anaerobes and intracellular pathogens.