Programmed cell death has long been recognized as an important mechanism of normal embryonic development. In the developing limb, massive programmed cell death apparently plays a critical role in controlling the amount of mesodermal tissue, sculpting overall limb shape, and defining the digits. Cell death in the limb bud has been shown to be regulated by a number of factors, including environmental conditions and epithelial-mesenchymal interactions. Removing the ectoderm overlying the interdigital region results in inhibition of cell death and ectopic cartilage formation in the subjacent mesenchyme. Recently, several signaling factors and genes have been implicated in the control of cell death in the limb bud. FGFs may acts as trophic factors that interfere with cell death. There is evidence that BMPs and Msx genes participate in regulating cell death. BMPs may in some cases trigger the cell death cascade, while Msx gene products regulate Bmp expression. A correlation between FGF, BMP and Msx in interdigital cell death is discussed.