The pathophysiology of median arcuate ligament syndrome (MALS) remains poorly understood with multiple pathophysiologic hypotheses, both vascular and neurogenic in origin. The median arcuate ligament (MAL) is a diaphragmatic structure of arch-like fascia linking the right and left diaphragmatic crura. When the MAL has a more caudal origin, it can cause compression of the celiac artery (CA). This compression is common, in up to 33% of the population, with a much smaller percentage experiencing symptoms, and found to have MALS. This compression can be exacerbated during the respiratory cycle, with the MAL traveling even more cranial during expiration. Compression of the CA impacts several routes of blood flow to the stomach, including the left gastric artery, the short gastric vessels (via the splenic artery), and the right gastric and gastroepiploic arteries (via the common hepatic artery). This relative gastric ischemia is one possible cause of pain in the epigastrium. In addition, the MAL can cause compression on the celiac plexus, resting above the CA, contributing to a neuropathic component of this syndrome. There are multiple etiologies for MALS that may be at play independently or in conjunction with one another, including CA compression, exacerbated by expiration, and compression of the celiac plexus, which can serve as targets for therapeutic intervention and further investigation.