Myocardial dysfunction frequently accompanies severe sepsis and septic shock. It is now clear that such a myocardial depression, as evidenced by biventricular alteration, is present during the early phase of sepsis in most patients. Myocardial depression exists despite a fluid loading-dependent hyperdynamic state and usually recovers within 7 to 10 days in survivors. Myocardial dysfunction does not appear to be due to irreversible structural abnormalities nor to myocardial hypoperfusion, but rather linked to many circulating mediators including cytokines. At a cellular level, reduced myocardial contractility could be related in part to apoptosis and induced by both nitric oxide-dependent and nitric oxide-independent mechanisms. However, whatever the mechanism involved, it leads to calcium homeostasis abnormality. The present review describes both the diagnosis procedure and the molecular and cellular pathways of sepsis-induced myocardial depression.