Obesity is closely associated with the development of type 2 diabetes. Many strategies have been used in the past to combat these two conditions, but very few provide for stable and durable glycemic control. Bariatric surgery has emerged as a powerful tool for treating obesity and in over 70 % of cases provides a short-term cure for diabetes. While the acute metabolic effects of surgery are striking, it remains important for us to also consider the long-term effects. This review aims to summarize the chronic or long-term metabolic and physiological effects of Roux-en-Y gastric bypass (RYGB) surgery on pancreatic function, skeletal muscle and hepatic insulin sensitivity, and gastrointestinal remodeling. An increased understanding of the current state of research in these areas can provide the basis for stimulating further research that would contribute to new treatment and management strategies for obesity and diabetes.