The pleural cavity is bathed by a small amount of physiologic fluid in health. More than 60 conditions can affect the pleura and disturb the equilibrium, resulting in significant accumulation of fluid from increased formation and/or reduced absorption of pleural fluid. Separating the fluid into transudates and exudates can triage investigations [1]. Transudates often arise from congestive heart failure and liver cirrhosis. Exudates are most commonly parapneumonic, malignant, or tuberculous in origin. An increasing number of biomarkers are now available, and many will likely be incorporated into the diagnostic algorithm in the future. Understanding the etiology of common causes of pleural effusion, their clinical presentation, fluid biochemistry, and clinical course is important to establish the correct diagnosis.