Type 1 diabetes (T1D) is an autoimmune destruction of insulin producing β-cells present in the endocrine part of the pancreas. Lifelong administration of exogenous insulin is a current mode of treatment, due to frequency of injection and precise dosing it remains a suboptimal treatment. Furthermore, this treatment fails to balance endocrine system and in prevention of severe complications associated with this disease. As immunotherapy approaches have remained unsuccessful, the only cure for T1D is transplantation of donor-derived pancreas or islets. However, donor scarcity, graft loss, and immune response to the foreign tissue are issues challenging this approach and limiting the number of patients who can benefit from such treatments. A recent estimate is that about 12,000 organ donors in the U.S. could potentially supply islets but that the number of donor preparations is likely only about 3,000 per year. This supply is unlikely to expand significantly in the future as a result b-cells replacement therapies are being considered as a means to treat T1D. Scientist are evaluating different sources of insulin-producing cells, including re-engineered human cells such as differentiated pluripotent stem cells and islets from other species. This presentation will summarize the cutting-edge research that aims to tackle the current challenges in reaching a quality-controlled product with long-term effects, with a focus on regenerative medicine approaches using different sources of b-cells.