This article reviews the difficulties in diagnosing and appropriately treating nosocomial pneumonias. Many disorders present with pulmonary infiltrates, fever, and leukocytosis that mimic hospital-acquired pneumonias. Aerobic gram-negative bacilli that reach the lungs by way of aspiration or bacteremia cause Nosocomial pneumonias. Staphylococcus aureus and anaerobes are not important pathogens in nosocomial pneumonia. Culture of respiratory secretions, regardless of technique, reflects the microbiology of proximal and distal airways, which is not proof of the isolates' pathogenicity in lung tissue. Culture of nonpulmonary pathogens or multiple pathogens from respiratory secretions is proof of specimen contamination. Respiratory secretion cultures do not differentiate colonization from infection and should not be the basis of antibiotic selection. Since respiratory secretion cultures are usually misleading, empiric monotherapy should be based on the most likely infectious pathogens, particularly Pseudomonas aeruginosa. Antibiotics selected for empiric monotherapy, or combination therapy, should possess a high degree of anti-Pseudomonas aeruginosa activity, have little or no resistance to potential, a good safety profile, and should be relatively inexpensive.