Gross aspiration of liquid or particulate matter into the lung can result in severe hypoxemia, pulmonary infiltrates in dependent lung regions, fever, and leukocytosis. The initial lung injury is primarily due to inflammatory mediators rather than infection. The responsible bacterial pathogens differ between community-acquired and nosocomial aspiration pneumonia. Many aspiration pneumonias are mixed aerobic-anaerobic infections. Enteric gram-negative bacilli and S aureus are more common in nosocomial aspiration pneumonia. Current treatment guidelines support initial empirical antibiotic therapy in patients with severe aspiration pneumonia pending culture results. Appropriate initial treatment improves outcome. Antimicrobial therapy for aspiration pneumonia is often empirical and should be based on patient characteristics, the setting in which aspiration occurred, the severity of pneumonia, and available information regarding local pathogens and resistance patterns.