Artificial manipulation of biochemical networks would be useful for the quantitative understanding of biological systems. Multiple methods have been suggested for controlling signal transduction, including light-induced dimerization (LID) and chemically induced dimerization (CID) systems. Of these, the LID system has strong advantages in terms of temporal and spatial manipulations. The photoresponsive proteins derived from fungi, cyanobacteria and plants and modified fluorescent proteins are used in this system. Recently, the authors developed a method for the efficient synthesis of phycocyanobilin, a chromophore of phytochrome B (PhyB), in cultured mammalian cells. This technique permits the LID system to be made with PhyB genetically encoded and manipulation of signal transduction with light of longer wavelength such as red and infrared light. This chapter discusses recent advances in the LID system, including a genetically encoded PhyB LID system, and its application to cultured cells and animals.