Whether due to occlusive or nonocclusive obstruction of the arterial inflow or obstruction of venous outflow, acute mesenteric ischemia (AMI) continues to be associated with high mortality rate. Early recognition based on a high index of suspicion is critical to early diagnosis and intervention, particularly among patients presenting with pain out of proportion to physical exam findings. In this episode, we discuss the pathophysiology of AMI, together with common causes, the initial clinical presentation, and management strategies for patients with this life-threatening and elusive surgical disease process.