Insulin receptor substrate 2 (IRS-2) is a key molecule in insulin signaling pathway, serving as an adaptor protein to insulin receptor to activate downstream kinase cascades, including MAP kinase and PI-3 kinase cascades. While reduced IRS-2 expression is tightly associated with diabetes and insulin resistance in various rodent diabetic models, this gene is also suggested to play a critical role in reproductive system and pancreas development. Recently, IRS-2 is demonstrated to be actively involved in lifespan regulation. In this chapter, we attempt to give a brief review of what we have learned about this molecule in metabolism and growth.