Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Over a relatively brief period of time, the respiratory fluoroquinolones have supplanted other first-line options as the predominant community-acquired pneumonia (CAP) therapy in hospitals. This article discusses the rise of the fluoroquinolone era, debates the comparative effectiveness of fluoroquinolones for CAP therapy, examines fluoroquinolone resistance and adverse drug reactions, and discusses new trends in pneumonia epidemiology and outcomes assessment. Overall, published data suggest that fluoroquinolone monotherapy is associated with improved patient survival compared with β-lactam monotherapy and similar survival to β-lactam plus macrolide combination therapy. Fluoroquinolone monotherapy may be associated with shorter hospital length of stay compared with β-lactam plus macrolide combination therapy, particularly in severe pneumonia or with high-dose therapy. There is insufficient evidence to conclude that any individual fluoroquinolone therapy is better than another with regards to patient mortality. Fluoroquinolones are generally well tolerated and Streptococcus pneumoniae resistance remains low; however, rare but serious adverse effects have been reported. Some members of the fluoroquinolone class have been removed from the market amidst safety concerns. Pneumonia classifications have changed and antipseudomonal fluoroquinolones may have a role in healthcare-associated pneumonia when administered in combination with other antipseudomonal and anti-methicillin-resistant Staphylococcus aureus therapies.