Septic shock involves a complex interaction between abnormal vasodilation, relative and/or absolute hypovolemia, myocardial dysfunction, and altered blood flow distribution to the tissues. Fluid administration, vasopressor support and inotropes, represent fundamental pieces of quantitative resuscitation protocols directed to assist the restoration of impaired tissue perfusion during septic shock. Indeed, current recommendations on sepsis management include the use of inotropes in the case of myocardial dysfunction, as suggested by a low cardiac output, increased filling pressures, or persisting signals of tissue hypoperfusion despite an adequate correction of intravascular volume and mean arterial pressure by fluid administration and vasopressor support. Evidence supporting the use of inotropes in sepsis and septic shock is mainly based on physiological studies. Most of them suggest a beneficial effect of inotropes on macro hemodynamics especially when sepsis coexists with myocardial dysfunction; others, however, have demonstrated variable results on regional splanchnic circulation, while others suggest favorable effects on microvascular distribution independently of its impact on cardiac output. Conversely, impact of inodilators on clinical outcomes in this context has been more controversial. Use of dobutamine has not been consistently related with more favorable clinical results, while systematic administration of levosimendan in sepsis do not prevent the development of multiorgan dysfunction, even in patients with evidence of myocardial dysfunction. Nevertheless, a recent metanalysis of clinical studies suggests that cardiovascular support regimens based on inodilators in sepsis and septic shock could provide some beneficial effect on mortality, while other one corroborated such effect on mortality specially in patients with proved lower cardiac output. Thus, using or not inotropes during sepsis and septic shock remains as controversy matter that deserves more research efforts.