It is common to see patients suffering from pleural effusion in clinics, and it is necessary to perform thoracocentesis to collect pleural effusion specimens for routine, biochemical, bacteriological as well as cytological tests for diagnostic and therapeutic purposes. Pleural effusion can be classified into transudate and exudate according to different pathogenesis and property, but the limitations of this taxonomy may bring misclassification of pleural effusion, thus more sensitive and specific examination items are urged to be established. To determine the property of pleural effusion correctly is precondition for effective treatment, as for now there’re lots of biomarkers in pleural effusion used to assist the diagnosis and differentiation of various diseases except for conventional tests. As a result of progress in biomedical techniques in recent years, more novel biomarkers are identified and verified in clinical decisions which make significant sense to etiology, diagnosis, discrimination and prognosis. Therefore, latest research advances of several biomarkers in pleural effusion will be briefly discussed in this essay.