Recent advance in molecular biology revealed new insights into the function of insulin receptor signalling and insulin receptor substrate (IRS) protein mediated signals in the central nervous system (CNS) in vivo. The IRS proteins mediate mainly intracellular effects of the insulin-like growth factor-1 receptor (IGF-1R) and the insulin receptor (IR). The functions of IRS proteins in peripheral tissues like muscle, liver, pancreas and fat have been characterised in detail. This book examines why IRS signalling is not only critical during brain development, but also for reproduction, energy homeostasis, ageing and possibly for neurodegenerative diseases in humans.