Actinomycosis and nocardiosis are uncommon pulmonary infections that share a similar predisposition to involve the pleural space. After establishment of an initial pneumonitis, infection spreads across lung fissures causing pleural thickening, pleural effusions, and empyema. Although less common in the antibiotic era, associated sinus tracts or subcutaneous abscesses may develop adjacent to pleural abnormalities. Both disorders most commonly present as chronic, debilitating illnesses with radiographic manifestations simulating lung cancer or tuberculosis; however, immunocompromised hosts may develop fulminant disease resembling acute bacterial pneumonia. Diagnosis depends on a high degree of suspicion so as to alert the microbiology and pathology laboratories to employ special methods to identify the organisms. The presence of pleural abnormalities in a chronic pulmonary condition is a diagnostic clue, and pleural fluid analysis may occasionally be the only means of confirming the diagnosis.