Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas frequently associated with metabolic causes, contributing factors, or consequences, including hypertriglyceridemia, obesity, and disorders of intermediary metabolism, respectively. To date, there is no specific therapy for this disease. Future optimal therapy should correct both inflammatory and metabolic components of the disease. Peroxisome proliferator-activated receptors (PPARs) are lipid-sensing nuclear receptors that control inflammatory and metabolic pathways via ligand-dependent and ligand-independent mechanisms. There are 3 known subtypes, PPAR-α, PPAR-β/δ, and PPAR-γ, which are differentially expressed in various tissues. The PPARs interact closely with other transcription factors such as nuclear factor κB and signal tranducers and activators of transcription that have pivotal roles in the pathobiology of AP. In this comprehensive review, we summarize the role of PPARs in AP, highlighting important in vitro and in vivo experimental findings. Finally, we propose future research directions as well as potential translational use of PPAR agonists in the treatment of AP.