The characteristics of recently developed oral fluoroquinolones include their broad spectrum involving gram-positive/gram-negative bacteria and atypical pathogens, potent antimicrobial activity against Pneumococcus, rapid tissue/sputum transfer, prolonged half-life, and reduction of their interaction with other agents. However, it has been reported that the common use of oral fluoroquinolones increases the number of fluoroquinolone-resistant bacterial strains. We review the appropriate use of these agents in patients with respiratory infections. In most cases, upper respiratory inflammation is a viral infection. Generally, antimicrobial agents are not necessary, and should not be administered. In Japan, a large number of antimicrobial agents, especially quinolones, are frequently prescribed to treat upper respiratory infection. This tendency must not be corrected. With respect to treatment for community-acquired pneumonia, it is controversial whether oral fluoroquinolones should be prescribed under various guidelines. In elderly patients and those with an underlying disease, oral fluoroquinolones may be a first-choice treatment at the outpatient clinic, because it is difficult to differentiate atypical pneumonia from bacterial pneumonia, and because the risk of drug-resistant Pneumococcus or gram-negative bacteria is high. With respect to treatment for hospital-acquired pneumonia, oral fluoroquinolones are recommended for patients with moderate or mild conditions without risk factors under the Guidelines established by the Japanese Respiratory Society. Bacteria causing acute infectious exacerbation in patients with chronic pulmonary diseases include gram-positive/gram-negative bacteria and anaerobic bacteria. Therefore, oral fluoroquinolones may be the most appropriate treatment for such patients. New oral fluoroquinolones show potent antimicrobial activity against tubercle bacillus, and may also be effective for infection with bacteria resistant to standard antitubercular agents. It may be controversial whether these agents should be indicated for atypical acid-fast bacterial infection.