2021 is the 100th anniversary of the discovery of insulin. The discovery of insulin not only reversed the fate of diabetic patients who died after diagnosis, but also promoted human understanding of protein biosynthesis, crystal structure, autoimmune diseases and precision medicine. Over the past 100 years, there have been 4 Nobel Prizes for research on insulin. Now, through a review recently published in Nature Medicine by Carmella Evans-Molina and others, we review the century-old history of insulin and the challenges we face in the future.