In non-cardiac ICU patients, the two major causes of acute myocardial dysfunction are sepsis-related cardiac depression (SRCD) and stress-related cardiomyopathy, the most common cause being the former. The main mechanisms responsible for SRCD include release of cardiac-depressant substances such as pro-inflammatory cytokines, hyporesponsiveness of beta-adrenergic receptors, decreased sensitivity of the myofilament to Ca++, and excessive production of perioxynitrite. Echocardiography is the best method to diagnose SRCD. If a cut-off value of 45% left ventricular ejection fraction is used to define SRCD, the occurrence of SRCD is 60% in septic shock patients (40% on the day of admission and in 20% the two following days). Recent advances in ultrasonography such as speckle-tracking (measuring the longitudinal systolic strain) may allow detecting cardiac abnormalities that are not detected by conventional echocardiography. Even when the SRCD is diagnosed, an important issue is to decide to treat it since left ventricular dilatation is an adaptive mechanism associated with a good outcome. The Surviving Sepsis Campaign suggests using dobutamine in patients who show evidence of persistent hypoperfusion despite adequate fluid loading and the use of vasopressor agents. In our opinion, it is more logical to give an inotrope when the shock state persists in the presence of: 1) proven SRCD with echocardiography and, 2) either low (mixed or central) venous blood oxygen saturation or increased veno-arterial carbon dioxide pressure gradient. Dobutamine is still recommended as the first-choice inotropic agent. Levosimendan is considered an alternative as it can restore the sensitivity of the cardiomyocyte myofilament to Ca++. Early administration of norepinephrine can not only increase blood pressure through an alpha1-adrenergic effect but also improve cardiac contractility through a beta1-adrenergic effect and/or an increase in the diastolic arterial pressure (i.e. the perfusion pressure of the left ventricle).