The Roman poet Horace was among the first to recognize that when “clogged with yesterday’s excess, the body drags the mind down with it.” Although considerable attention has been paid in neuroscience to the enhancement of neuronal function by wheel running and caloric restriction, far less is known about the other side of this issue. What are the consequences of unhealthy habits to central nervous system function? Prolonged exposure to excessive caloric intake impairs neuronal function and also contributes to obesity and other risk factors for diabetes. Diabetes, a disease characterized by reduced sensitivity to glucose and insulin, is also associated with deficits in brain structure and function. In contrast, enhancement of somatic metabolism by wheel running or caloric restriction improves central neuroplasticity. Generalizing across studies reveals a relationship between global metabolic efficiency and neuroplasticity in the hippocampus, a brain region that is essential for learning and memory. The specific principles upheld by these findings are suggestive of a continuum, with global metabolic alterations fluctuating in concert with neuroplasticity in the hippocampus.