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Publisher Summary This chapter deals with the paradigm of cell signaling. It uses the nomenclature to annotate the classes of molecules involved in cell signaling. It also lists signaling pathways and explains their role in tissue homeostasis and tissue engineering. The molecular mechanism by which cells communicate, referred to as cellular signaling are discussed. Cellular signaling is initiated by generation of a ligand; i.e. a molecular entity generated by a sending a cell to bring about a change in the physiology of a responding cell. A central paradigm can be recognized in most events of cellular signaling, which consists of three distinct steps: signal initiation, signal transduction, and gene activation. The chapter defines that signaling pathways are regulated at many different levels, i.e. extracellularly, in the cytoplasm and in the nucleus. This provides engineers multiple means to manipulate the cell appropriately.