Acute pericarditis is not uncommon in clinical practice and may occur either as isolated disease or as a manifestation of another disease (known or still unknown). The etiology is varied and complex and a clinically-oriented approach to management is possible by identifying initial presentation features of high risk (risk of complications or specific disease: fever >38°C, subacute course without acute chest pain, large pericardial effusion, cardiac tamponade, and lack of response to empiric anti-inflammatory therapy), that suggest admission and additional diagnostic evaluation. In any case, a prompt anti-inflammatory therapy at full doses till remission is warranted to prevent complicated and prolonged courses. In this paper, we will try to clarify common doubts and outline evidence-based approaches to the diagnosis, therapy and follow-up of these patients.