The appropriate use of the clinical microbiology laboratory for diagnosing lower respiratory tract infections is controversial. As in clinical care, it is crucial to categorize the presenting illness properly as acute bronchitis, an acute exacerbation of chronic bronchitis, community-acquired pneumonia, or nosocomial pneumonia if diagnostic efforts to establish a microbial etiology are to be productive for the individual patient and affordable to society. The greatest potential benefit of microbiological investigations lies in the etiologic diagnosis of pneumonia. For community-acquired pneumonia, evaluation of a gram-stained smear of sputum in terms of both quality and microorganisms present can help guide initial therapy as well as aid interpretation of subsequent culture results. As discussed in this review, the role of the clinical microbiology laboratory in the etiologic diagnosis of nosocomial and complicated pneumonias is more extensive and, in addition to evaluation of respiratory secretions, may include cultures of blood, pleural fluid, and specimens obtained by bronchoscopy. However, a prerequisite for the use of all currently available tests is their deployment for patients with clinical and radiographic evidence of pneumonia.