This review outlines the history, physiology, clinical circumstances, pharmacology, pitfalls and proper implementation of exogenous pancreatic enzyme replacement therapy (PERT). Humanity has used PERT for hundreds of years--but in the last 30-50 years with much improved precision. Some topics that will be reviewed here include the complex diagnosis, prevalence, and long-term complications of Exocrine Pancreatic Insufficiency (EPI) and resultant dysfunction in Digestive Capacity (DC). The indications, efficacy, and safety of PERT in Exocrine Pancreatic Insufficiency (EPI). Optimizing PERT is not as easy as it seems. Many practical tips for PERT optimization are outlined for the reader.