Bacterial respiratory tract infections (RTIs), whether primary or subsequent to viral infection, are a frequent cause of morbidity and mortality worldwide. Treatment of these infections is most often empirical. Therefore, an antimicrobial’s antibacterial spectrum must include the most likely pathogens: <i>Streptococcus pneumoniae, </i>the most frequent cause of community-acquired pneumonia (CAP), <i>Haemophilus influenzae</i>, <i>Moraxella catarrhalis</i>, and <i>Staphylococcus aureus</i>, as well as atypicals such as <i>Mycoplasma pneumoniae</i>, <i>Legionella pneumophila</i> and <i>Chlamydophila (Chlamydia) pneumoniae</i>. In addition, knowledge of antimicrobial resistance among these key pathogens is imperative for physicians to choose the most appropriate therapeutic agent. The latest data from global surveillance studies indicates that high-level resistance to penicillin (MIC ≧2 mg/l) among isolates of <i>S. pneumoniae</i> varies widely by geographic location. Rates exceed 20% in the USA, Mexico, Japan, Saudi Arabia, Israel, Spain, France, Greece, Hungary, and the Slovak Republic. In South Africa, Hong Kong, Taiwan, and South Korea rates exceed 50%. Penicillin non-susceptibility – including isolates exhibiting high-level resistance and intermediate susceptibility (MIC 0.12–1 mg/l) – is frequently found in association with macrolide resistance, which is found at a prevalence of 70–80% in some Asian countries. Trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline resistance, either individually or combined with macrolide resistance as multiple resistance, is also associated with reduced susceptibility to penicillin. Another concern about antimicrobial resistance in respiratory tract pathogens is β-lactamase production among isolates of <i>H. influenzae </i>and <i>M. catarrhalis</i>. However, respiratory fluoroquinolones, of which levofloxacin has been available for the longest time, currently remain active against the great majority of common bacterial respiratory pathogens, including atypicals.