Both type I and type II diabetes are common diseases with no cure. Both are characterised by chronic hyperglycaemia and can be managed, at least to some extent, by daily proteins treatments. However, in both cases, administration of the protein does not always control glucose levels in a physiologically normal time frame. A variety of different approaches to restore lost insulin in type 1 diabetes by gene therapy have recently been described. Strategies to induce production of new β cells, ameliorate or evade the auto-immune response that leads to β cell destruction, or simply delivering a modified insulin cDNA under the control of glucose-responsive promoters have all resulted in restoration of euglycaemia in a physiologically normal time frame in rodent models of diabetes. In terms of application of gene therapy to type 2 diabetes, delivery of a single protein using a virus vector can also restore euglycaemia in vivo. In addition to these advances, new technologies to permanently modify the genome which could be adapted for the long-term treatment of diabetes are described.