This chapter argues that the major role of the nervous system involves initiating actions in response to challenges in the environment. In humans, the most important system for control of activity of the skeletal muscles starts in the motor area of the cerebral cortex, which in humans lies just in front of the central sulcus. A large fiber tract, called the cortico-spinal tract, connects the motor cortex with the spinal cord. The primary motor cortex is the source of most of the cortico-spinal axons, but its activity is strongly influenced by the pallidum, striatum, cerebellum, and many other cortical regions, including the somato-sensory area of the cortex. The brain translates these high-level plans into the initiation of contraction of dozens of muscles needed to carry out the required movements. All motor control systems act through alpha motor neurons, which are the final pathway to muscles. These motor neurons in the ventral horn of the spinal cord activate the skeletal muscles of the limbs and trunk.