Incredible strides have been made since the discovery of insulin almost 100 years ago. Insulin formulations have improved dramatically, glucose levels can be measured continuously, and recently first-generation biomechanical "artificial pancreas" systems have been approved by regulators around the globe. However, still only a small fraction of patients with diabetes achieve glycemic goals. Replacement of insulin-producing cells via transplantation shows significant promise, but is limited in application due to supply constraints (cadaver-based) and the need for chronic immunosuppression. Over the past decade, significant progress has been made to address these barriers to widespread implementation of a cell therapy. Can glucose levels in people with diabetes be normalized with artificial pancreas systems or via cell replacement approaches? Here we review the road ahead, including the challenges and opportunities of both approaches.