The functional reprogramming of a differentiated cell to pluripotency may present beneficial applications in regenerative medicine. Somatic cell nuclear transfer may offer this possibility, but technical hurdles and ethical guidelines currently prevent application of this technology in several countries. As a result, alternative approaches are being developed for altering cell fate. Recent non-nuclear transfer-based approaches for reprogramming somatic cells are discussed as well as ways to enhance their differentiation potential. These approaches include the fusion of differentiated cells with embryonic stem cells and the use of extract from pluripotent cells to reprogramme differentiated cells into multipotent or pluripotent cells.