Embryonic stem cells are by definition the master cells capable of differentiating into every type of cells either in vitro or in vivo. Several lines of evidence suggest, however, that adult stem cells and even terminally differentiated somatic cells under appropriate microenvironmental cues are able to be reprogrammed and contribute to a much wider spectrum of differentiated progeny than previously anticipated. This has been demonstrated by using tissue- specific stem cells, which like embryonic stem cells do not express CD45 as an exclusive hematopoietic marker (skin, adipose, cord blood and bone marrow- derived stem cells). On the other side, there is a great number of reports which demonstrate that hematopoietic cells (CD45+) from different sources (peripheral blood, cord blood, bone marrow) are also able to cross the tissue boundaries and give rise to the cells of the other germ layers. Herein we discuss the differentiation and reprogramming potential of both hematopoietic and non- hematopoietic stem cells along endodermal, mesodermal and neuroectodermal lineage and their importance for regenerative medicine.