This chapter demonstrates that the relationship between exercise and the nervous system is not limited to the musculoskeletal and motor performance dimensions, but is built upon a multilayered neurobiological foundation that encompasses neuronal structure, synaptic transmission, neurotransmitter balance, neurotrophic factors, and neuroplasticity. The macro-level organization of the nervous system (central and peripheral nervous systems; somatic and autonomic subsystems) and its micro-level dynamics (dendrite–axon integrity, action potential, synaptic plasticity) are reshaped through exercise. While increased motor commands during exercise are transmitted to skeletal muscles via the somatic nervous system, sympathetic activation at the level of the autonomic nervous system and parasympathetic/vagal responses during recovery regulate cardiovascular and respiratory adaptations. Neurotransmitters (dopamine, serotonin, noradrenaline, GABA, glutamate) and neurotrophic factors (particularly BDNF, IGF-1, VEGF) together provide a neurobiological basis that, through exercise, enhances attention, executive functions, memory, mood, and stress-coping processes. From a lifespan perspective extending from childhood to older adulthood, regular physical activity plays a critical role in cognitive development, academic adjustment, motor skills, cognitive flexibility, and protection against neurodegenerative processes. In conclusion, this chapter positions exercise as a powerful neurobiological intervention that supports the structural flexibility and functional capacity of the nervous system and promotes brain health, and which, when integrated with measurement- and monitoring-based programs, ensures the sustainability of both performance and mental well-being.