Acute or fulminant nonischemic, dilated cardiomyopathy (DCM) is an uncommon cause for heart failure with a highly variable prognosis that is in part dependent on histopathology and in part on clinical presentation. Once common causes of acute DCM are excluded using standard clinical tests, the specific inflammatory and infectious causes of DCM should be systematically evaluated and treated. Specific histopathologic forms include fulminant lymphocytic myocarditis, which has an excellent prognosis with standard heart failure care. By contrast, giant cell myocarditis, which may be fulminant or acute, has a poor prognosis and frequently requires heart transplantation or immunosuppression for long-term survival. Noninvasive tests that may support the diagnosis of fulminant or acute myocarditis include cardiac magnetic resonance imaging and biomarkers of cardiac injury. Certain clinical, hemodynamic, and echocardiographic variables predict risk of death or transplant in acute myocarditis. This article will compare the presentation, prognosis, and treatment options for several uncommon causes for acute heart failure and suggest certain clinical scenarios in which the likelihood of specific histopathologic disorders is high enough to warrant endomyocardial biopsy if noninvasive tests are inconclusive.