Dysfunctioning of the heart forms part of the multiple organ dysfunction syndrome (MODS) in sepsis and SIRS. This acute septic cardiomyopathy is often underestimated in degree and relevance, although yet in fact 10% of all sepsis fatalities are due to intractable heart failure. This potentially reversible cardiomyopathy is characterized by a considerable pump failure, is not primarily ischemic, coronary blood flow being normal or even enhanced; left and right ventricle are enlarged as a consequence of an increased ventricular compliance. Damage of the heart can further be aggravated in case of an additional right ventricular impairment due to pulmonary hypertension in ARDS. SIRS-cardiomyopathy in non-infectious MODS has common traits with acute septic cardiomyopathy. The pathogenesis of heart disease in sepsis and SIRS is multifactorial, the endotoxin/TNF-alpha/NO/cGMP-cascade representing a main negative inotropic axis. Therapy of acute septic cardiomyopathy and SIRS-cardiomyopathy at present still is mainly symptomatic (volume substitution, inotropic/vasoactive agents), causal therapeutic principles are, however, put to test in the context of a comprehensive concept of causal sepsis treatment.