Respiratory tract infections (RTIs) are the most common, and potentially most severe, of infections treated by health care practitioners. Lower RTIs along with influenza, are the most common cause of death by infection in the United States. Risk factors for pneumonia and other respiratory tract infections include: extremes of age (very young and elderly), smoking, alcoholism, immunosuppression, and comorbid conditions. The microbial cause of RTIs vary depending on the infection (i.e., pneumonia compared with acute bacterial sinusitis), setting (i.e., community-acquired compared with nosocomial), and other factors. The causative pathogens associated with CAP have changed in prevalence over time. Although Streptococcus pneumoniae remains the most common causative pathogen, a number of newer pathogens, such as Chlamydia pneumoniae and sin nombre virus, have been recognized in recent years. The emerging antimicrobial resistance of respiratory pathogens (most notably S. pneumoniae) has also increased the challenge for appropriate management of RTI. An awareness of the epidemiology and cause of specific respiratory infections should optimize care.