Acute pancreatitis (AP) is a common and destructive inflammatory condition of the pancreas. Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has become the second major cause of AP. Although the association between HTG and AP is well established, HTG as a risk factor of AP in the general population is not well identified. In this review, we summarize recent progress in our understanding of the pathogenesis of HTG-AP and clinical management of this disease. The mechanism responsible for HTG-AP is related to high-level free fatty acid (FFA), microcirculatory disorder, oxidative stress, Ca2+ overload, and genetic polymorphism. Heparin and insulin therapy in diabetic patients with HTG can dramatically reduce triglyceride levels. Use of plasmapheresis is still experimental and better-designed studies are needed to evaluate the promise in the management of HTG-AP. Dietary intervention, lifestyle changes, and control of secondary causes are critical to the management and treatment of HTG-AP.