Severe sepsis is a complex syndrome often resulting in multiple organ dysfunction. This is an extremely challenging problem to manage in the intensive care unit, with mortality rates remaining at unacceptably high levels. Death of patients afflicted by this condition generally results from organ dysfunction syndromes related to hypoperfusion abnormalities. Management of patients with severe sepsis or septic shock can be very complex and challenging, utilizing a significant amount of resources. Pharmacologic support of patients with severe sepsis or septic shock primarily involves agents to support and improve perfusion at the microvascular level. It is important to understand the pharmacologic properties of the medications utilized to manage patients with these conditions. The information presented in this article is based on the best evidence currently available in order to assist the critical care nurse in understanding the pharmacologic therapy related to treatment of severe sepsis and septic shock.