Pericardial effusion is a known complication of many advanced malignancies, with strong impact both on quality of life and prognosis. The initial and easier relief can be obtained through percutaneous pericardiocentesis, echo- or fluoro-guided. However, effusion recurrences can be observed in up to 40% of cases. Effective management can be obtained by more invasive approaches like percutaneous or surgical creation of pericardial windows but the more cost-effective procedure is pericardiocentesis followed by intrapericardial instillation of sclerosing or cytostatic agents like tetracyclines, bleomycin, cisplatin and thiotepa. No significant local or systemic side effects are reported, except for chest pain during tetracyclines instillation. No recurrences at 30 days are observed in 80%-90% of patients, according to different series and, particularly, to different malignancies. No evidence-based data are in fact available to assess the "gold standard" and the best therapeutical approach for the single patient.