Mycobacterium tuberculosis (TB) infection of the pleural space is an important cause of pleural effusion in areas of high TB prevalence. Microbiological analyses of pleural fluid in the acute setting may be negative. Consequently, investigations may proceed to more invasive techniques, such as pleural biopsy or thoracoscopy. Ongoing research has led to implementing a number of additional fluid analyses that may lead to a diagnosis without a need for further invasive procedures. In this review, we discuss the characteristics of tuberculous pleural fluid that may assist in this important diagnosis, and we highlight the benefits of specific biomarker analyses. English-language publications from a MEDLINE search and references from relevant articles from January 1, 1990 to September 1, 2009 were reviewed. The key words searched included tuberculosis, pleural fluid, effusion, diagnosis, adenosine deaminase, and interferon.