The aim of this review is to deal with management challenges related to diagnosis and therapy of noninfectious pericarditis. In the European countries in which a low prevalence of tuberculosis is noted, determining the etiology of pericarditis is essentially aimed at the exclusion of the most common causes, which may require a specific therapy and are associated with an increased risk of complications: systemic autoimmune or autoinflammatory diseases, postcardiac injury syndrome (5%-20%), neoplastic pericardial involvement (5%-10%), tuberculosis (about 5%), and rarely purulent pericarditis in less than 5% of cases. In developing countries that report a high prevalence of tuberculosis, this condition is the most common cause of pericardial diseases. The diagnosis is based on clinical criteria (pericarditis‑related chest pain and pericardial rubs) complemented by laboratory (elevated levels of C‑reactive protein) and imaging findings (electrocardiography, echocardiography, and other imaging modalities to provide evidence of pericardial inflammation in doubtful cases). Poor prognostic predictors (high fever >38 °C, subacute course, large pericardial effusion, cardiac tamponade, and lack of response to empiric anti‑inflammatory therapies) identify high‑risk patients who should be admitted to the hospital in order to determine disease etiology and receive appropriate treatment. The mainstay of medical therapy of noninfectious pericarditis is based on nonsteroidal anti‑inflammatory drugs and colchicine, with possible adjunct of corticosteroids at low‑to‑moderate doses in unresponsive patients. Additional therapies, particularly with anakinra, have been implemented for those who develop corticosteroid dependence and are colchicine‑resistant. Disease recurrence is the most common and troublesome complication of pericarditis, whereas the risk of developing constrictive pericarditis is related to the etiology and not to the number of recurrences.