Multisystem inflammatory disease in children (MIS-C) is a condition typically seen 3 to 6 weeks after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Believed to be a postinfection hyperinflammatory response, the clinical manifestation of this viral sequelae can vary significantly in severity and symptomatic presentation. Clinical prodrome includes persistent fever and dysfunction of at least two organ systems. Often developing after asymptomatic or mildly symptomatic coronavirus disease 2019 (COVID-19) infection, MIS-C is a diagnosis of exclusion that requires evaluation for other infectious or noninfectious etiology for symptoms. Vital sign instability, including fever, tachycardia, and hypotension; laboratory studies demonstrating elevated inflammatory markers and elevated cardiac markers; and positive SARS-CoV-2 polymerase chain reaction, SARS-CoV-2 antibodies, or exposure to someone with confirmed COVID-19 infection 4 to 6 weeks before clinical presentation are used to diagnose this condition. Skin and mucosal involvement, gastrointestinal symptoms, and neurologic manifestations are also commonly seen. An echocardiogram is indicated to evaluate for cardiac dysfunction, including but not limited to coronary artery enlargement, left ventricular dysfunction, arrythmias, or atrioventricular block. [Pediatr Ann. 2023;52(3):e114-e121.].