Sepsis accounts for more than 210,000 deaths per year. Despite adequate fluid resuscitation the associated maldistribution of blood flow may cause an imbalance between oxygen delivery and demand, leading to global tissue hypoxia, shock, and, if not reversed, death. Vasoactive therapies including catecholamine and noncatecholamine vasopressors, ionotropes, and vasodilating agents aimed at restoring perfusion and normalizing oxygen consumption have improved outcomes in patients with persistent shock despite crystalloid resuscitation. In this review we discuss the mechanisms, clinical use, and commonly observed pitfalls of the most common and a few uncommon vasodilator agents used in the management of sepsis and septic shock.