Percutaneous drainage is the default strategy for evacuating a pericardial effusion. A pericardiocentesis can be necessary or required in a wide variety of clinical settings ranging from urgent tamponade to relieve in iatrogenic hemorrhagic effusions in the electrophysiology or catheterization room, to planned diagnostic procedures in patients with suspected or known malignancy or infections. With the help of several procedural improvements over the past decades, echocardiography and fluoroscopy-guided percutaneous pericardiocentesis has become the standard intervention for evacuating pericardial effusions, as well as an essential tool in the diagnostic work-up of an unexplained pericardial effusion. When performed by skilled physicians assisted by appropriate imaging it is a very safe procedure, and provided that an indwelling catheter is placed, it is also very effective with an acceptably low risk of recurrences. In this review, the indications and standard techniques for pericardiocentesis are discussed, as well as their consequences for patients with iatrogenic and malignant effusions.