The co-existence of pulmonary hemorrhage and glomerulonephritis delineates a severe syndrome, often underestimated, resulting from several diseases and frequently associated with serum positivity for antineutrophil cytoplasmic antibodies (ANCA) or antiglomerular basement membrane (GBM) antibodies. The most common illness presenting as pulmonary-renal syndrome is systemic vasculitis. Moreover, the idiopathic pulmonary-renal syndrome is a distinctive clinicopathologic entity with different pathogenetic mechanisms. Tissue immunofluorescence studies are fundamental in distinguishing anti-GBM antibody-mediated forms from immune-complex-mediated and ANCA-associated forms. The type of glomerular or alveolar immunologic injury is the main factor determining the outcome and thus the prognosis of the pulmonary-renal syndrome. Development and improvement of appropriate serologic detection techniques have given reliable and early guidance for diagnosing these cases.