The differential diagnosis of ascites often leads to confusion and an inability to exclude its multitude of causes in many patients. In this review, we outline the clinical features and laboratory investigations that usually elucidate the cause of ascites for the clinician in a simple and logical manner. Roughly 80-85% of cases of ascites are related to underlying chronic liver disease, but cardiac failure, tuberculosis, malignancy-related ascites and other less common causes should always be considered. Careful evaluation of the patient, including a clinical history, physical examination and diagnostic paracentesis should routinely be performed to determine the cause of ascites. Fluid should be sent for cell count and albumin along with simultaneous determination of serum albumin to determine the serum: ascites albumin gradient. This gradient allows classification of the cause of ascites into portal hypertension-related and nonrelated with a diagnostic accuracy of > or = 97%. The causes of ascites are individually discussed in relationship to their clinical features and to the laboratory investigations that are relevant in each situation.