Constrictive pericarditis (CP) is a challenging clinical scenario in which the heart muscle is entrapped by thick, fibrous, and frequently calcified pericardial layers. Whereas infectious diseases (mostly bacterial) had been observed as the main etiology in the last decades, nowadays, post-surgical or radiotherapy iatrogenic inflammation is becoming highly prevalent with the exception of developing countries and patients with immunodeficiency in which tuberculosis is still frequently observed. Clinically, progressive dyspnea and peripheral edema are present and frequently considered of unknown origin because of the diagnostic challenge that CP poses. As a matter of fact, a specific knowledge of echocardiography and right heart catheterization is essential to recognize constriction features. Moreover, a valuable support is provided by dedicated imaging modalities (mostly magnetic resonance). Complete surgical removal of the pericardium (pericardiectomy), when feasible and performed early, is associated with excellent symptomatic improvement. Unfortunately, in specific scenarios (radiation therapy) or when surgery is performed after severe constriction development, surgical outcomes are poor, and CP assumes the profile of an end-stage disease. This reinforces the unmet need of early detection of CP and the development of novel therapeutic strategies.