Intracrine peptides and proteins participate in the regulation of adult and pleuripotential embryonic-like stem cells. Included among these factors are VEGF, dynorphin, AChE-R, Oct3/4, Pdx-1, Pax-6, and HMGB1 among others. In some cases the establishment of intracrine feedback loops can be shown to be relevant to this regulation consistent with previously proposed principles of intracrine action. Here the role of intracrines in stem cell regulation is reviewed with particular attention to the intracrine regulation of cardiac stem cells. The reprogramming of cells to restore the pleuripotent phenotype and the possible role of stem/progenitor cells in neoplasia are also discussed.