Epidemiological studies demonstrated positive effects of continuous physical activity and balanced diet on cardiovascular fitness. In chronic neurodegenerative disorders, e.g. Parkinson's disease and Alzheimer's disease, physical activity has become a successful supportive symptomatic therapy. However, it has become evident that physical activity not only improves motor symptoms but also has high impact on cognition in both (elderly) healthy brain and neurodegenerative alterations in the CNS. Nutrition also has been reported to exert positive effects on brain function.Animal studies indicate an increased endogenous plasticity as the underlying mechanism in terms of activation of neuronal precursor cells in different brain areas, leading to improved brain function.First experimental studies in humans also show that physical activity and balanced nutrition increase the release of neurotrophic factors in the brain, increase the volume of grey matter in learning- and memory-associated brain regions and improve cognitive function. This phenomenon opens up noninvasive causal therapeutic options in neurodegenerative disorders and during aging-associated cognitive decline by inducing changes in lifestyle. This option could provide a socioeconomically and ethically reasonable treatment for neurodegenerative disorders.The presented article summarizes the current knowledge from animal experiments and studies in humans. It provides an overview of potential cellular and molecular candidate mechanisms and discusses novel translational clinical studies and first clinical applications.