**Abstract**

The pathophysiology of diabetes is related to the levels of insulin within the body, and the body's ability to utilize insulin. Patients with diabetes persistently go through life-threatening hypoglycaemia. Consequently, their quality of life gets affected, progressively leading them to micro- and macro-vascular complications. This is an unmanageable happening despite the technology advancements in insulin formulations. Nevertheless, islet transplantation is emerging as an alternative therapeutic option. Our chapter will elaborate on the recent advancements in this field highlighting the present-day challenges of clinical islet cell transplantation. Additionally, details about the advancements in cutting-edge clinical research, bio-molecular signaling with special reference to the pre and post transplant, the need for beta-cell replacement therapies, including the application of induced pluripotent stem cells and mesenchymal stem cells are also mentioned in this chapter.

**Keywords:** diabetes, β cell, islet transplantation, human pluripotent stem cells (PSCs), PSC-derived islet cells, immunosuppressant
