For patients with chronic pancreatitis whose pain is inadequately controlled with opiate analgesia, surgical resection offers a good chance of symptomatic relief. However, the inevitable sequela is type 1 diabetes mellitus and its attendant long-term complications. Islet cell autotransplantation offers a theoretical "cure" for this iatrogenic diabetes but this end point has not been produced consistently in clinical practice. The main factor determining the likelihood of insulin independence after islet autotransplantation is the islet mass that is transplanted. This review examines the factors that affect the functional islet mass available for transplantation. Original articles and reviews from peer-reviewed journals were analyzed following a computer search of the MEDLINE database from 1966 to the present, we extracted mainly level 2 and level 3 data. Although improvements in collagenase consistency and purification techniques and reductions in cold ischemic times have all been shown to improve islet yield, there is still the need to optimize every stage in the islet isolation process. Increasing the proportion of potential islets in the final isolate is of particular importance in chronic pancreatitis because the total mass of islets initially available in the gland might be just sufficient to produce insulin independence after islet autotransplantation. We believe that reducing the warm ischemic time might significantly increase the likelihood of insulin independence after islet autotransplantation.