Sepsis is associated with cardiovascular changes that may lead to development of tissue hypoperfusion. Early recognition of sepsis and tissue hypoperfusion is critical to implement appropriate hemodynamic support and prevent irreversible organ damage. End points for resuscitation need to be defined and invasive hemodynamic monitoring is usually required. Targets for hemodynamic optimization should include intravascular volume, blood pressure, and cardiac output. Therapeutic interventions aimed at optimizing hemodynamics in patients with sepsis include aggressive fluid resuscitation, the use of vasopressor agents, inotropic agents and in selected cases transfusions of blood products. This review will cover the most important aspects of hemodynamic optimization for treatment of sepsis induced tissue-hypoperfusion.