A number of studies have confirmed that gene therapy can be successfully applied to prevent type 1 diabetes mellitus and to facilitate the transplantation of replacement insulin-producing cells as allografts of the islets of Langerhans or in the form of enriched and homogeneous surrogate cells. However, these successes have remained restricted to a few rodent models and have not progressed past this stage into larger animals. Newer technology has also emerged that offers exciting alternatives or complementary methods to achieve the same results, including therapeutic cloning. A synopsis of the strategies and tools used successfully in vivo is provided and a proposal to motivate a step-up of these approaches to larger animals, if not outright to safety trials in humans, is outlined. Additionally, newer emerging technologies that can, in the future, complement those that are currently readily adaptable to clinical implementation are suggested.