Thoracentesis is defined as drainage of fluid from the pleural cavity. It can be safely performed at a patient’s bedside, office or procedure unit, or radiology suite. The most common indication is evaluation of a new pleural effusion of uncertain etiology. The major contraindication of the procedure is bleeding disorders, including various types of coagulopathies, thrombocytopenia, and administration of anticoagulants. The purpose of this chapter is to review in more detail the indications and contraindications for thoracentesis, give a brief review of pleural fluid evaluation, and explain the techniques of how the procedure is performed.