Despite being categorized as a procedure associated with a low risk of iatrogenic hemorrhage, percutaneous pleural drainage in patients taking the ubiquitous antiplatelet agent clopidogrel is still commonly perceived as a risky proposition. There is mounting evidence, however, in support of the safety of percutaneous needle procedures in persons receiving this medication. Establishing that these pleural interventions can be performed safely without clopidogrel interruption would be of great clinical significance, especially in those taking it for recent cardiac stenting and therefore in danger of stent thrombosis should antiplatelet therapy (APT) be withheld. The purpose of the present review is to summarize the available data from published studies and series of thoracentesis and chest tube insertion in patients exposed to clopidogrel. Also incorporated into this review are relevant investigations from the thoracic surgery and interventional radiology experience, which contribute indirect evidence and help shape the context for interpreting the safety data reported in the pleural literature. At the end, an attempt is made to synthesize the current knowledge on this topic into conclusions for guiding practice.