The development of cell and organ transplantation is one of the great success stories of modern medicine. Transplantation of various cells, tissues, and solid organs has entered the realm of the clinically routine. 1-4 Milestones in cell therapy include the development of transfusion medicine, hemopoietic stem cell transplantation, and adoptive immunotherapy. Progress in cell therapy outside hematology has been slower to develop, but recent progress has been made in Parkinson disease5, 6 and diabetes mellitus. 7 Most recently, advances in stem cell biology may presage an impending revolution in cell therapy. Several studies have demonstrated that the stem cells of healthy adults retain enormous plasticity. For example, hemopoietic stem cells can differentiate into muscle, 8, 9 liver cells, 10 and neurons11, 12; neural stem cells can differentiate into blood, 13 liver, kidney, or muscle cells14; and muscle stem cells can differentiate into blood. 15 Human embryonic stem cells, which are capable of contributing to all human tissues, have been generated for the first time. 16 These discoveries make imaginable the prospect of developing a new generation of cell therapeutics applicable to a vast array of diseases. However, before this vision can be realized many obstacles must be overcome, with one of the most important obstacles resting in the present inability to control what happens to a cell after it has been transplanted. Currently available tools for controlling the survival, growth, and differentiation of transplanted cell populations are blunt instruments. In most cases, graft-versus-host disease (GVHD) is only poorly controlled with immunosuppressive drugs, which in turn cause a punishing array of side effects. Lineage-restricted growth factors such as erythropoietin and granulocyte colonystimulating factor (G-CSF) have had a major effect on clinical hematology, but growth factors are powerless in situations in which it is desirable to preferentially expand a subpopulation of cells with a particular lineage. These situations may arise in the setting of mixed chimerism, in which donor and host hemopoietic elements coexist; or in gene therapy, in which only a fraction of cells contain the therapeutic gene. Under these circumstances, it would be useful to have a means of specifically influencing the in vivo behavior of genetically modified cells in terms of proliferation, death, or differentiation. Toward this end, conditional systems have been developed that rely on the principle that protein interactions control virtually all cellular processes; in particular, protein dimerization (or oligomerization) is at the heart of many signaling pathways controlling cell death, proliferation, and differentiation. These conditional systems share 2 main components: a fusion protein and a drug. The fusion protein contains an intracellular signaling molecule linked to a protein that provides a high-affinity binding site for a drug called a chemical inducer of dimerization (CID). Individually the signaling domains are functionally inert. Activation occurs upon bringing 2 signaling domains into close proximity with one another, a process termed dimerization. Proximity is controlled through addition of the CID, which in turn activates signaling. The signaling fusion thus serves as a switch that is turned on in the presence of the CID and off following withdrawal of the CID. This method has the potential to control the behavior of genetically modified cells both in vitro and in vivo. The generation of pharmacologically regulated alleles has important implications for analyzing the effect of signaling molecules such as growth factor receptors, Janus kinases (JAK), signal transducers and activators of transcription, and …