Acute pancreatitis is a common inflammatory disorder of the pancreas resulting in considerable morbidity and a mortality rate of approximately 5%. Although there are no pharmacologic treatments known to improve important outcomes, aggressive intravenous fluid resuscitation generally is recommended in all patients. However, few human investigations have been performed and several important questions have not been answered. For example, what is the optimal resuscitative fluid? Is there a role for colloid solutions? To what clinical marker should resuscitation be targeted? When is the best time to start such fluids and in which group of patients? This review describes the microcirculation of the pancreas and the pathophysiologic alterations caused by acute pancreatitis. Previous animal experiments are described, as are the limited human studies specifically addressing fluid resuscitation. Finally, current recommendations and goals for further investigation are highlighted. It is our hope that this review will stimulate interest in this often overlooked subject and lead to carefully designed human clinical trials using varying fluid solutions and rates, with an emphasis on patient monitoring and safety, in the near future.