In most diseases related to pleural effusion, the fluid analysis yields important diagnostic information, and in certain cases, fluid analysis alone is enough for diagnosis. The many important characteristics of pleural fluid are described, as are other complementary investigations that can assist with the diagnosis of common and rare pleural effusions. For a systematic review of pleural effusion, a literature search for articles on the practical investigation and diagnosis of pleural effusion was done. Articles included guidelines, expert opinion, experimental and nonexperimental studies, literature reviews, and systematic reviews published from May 2003 through June 2009. The search yielded 1 guideline, 2 meta-analyses, 9 literature reviews, 1 randomized control trial, and 9 clinical studies. On the basis of class IIa or class I evidence from these articles, a step by step approach is recommended for investigating a pleural effusion, beginning with assessment of the medical history, clinical examination, radiology, pleural fluid evaluation, and finally, if no diagnosis is forthcoming, a pleural biopsy under image guidance or thoracoscopy.

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