Natural selection defined our genotype as athletes who sleep 8-9 h each night. Physical activity and sleep exhibit positive synergy, whereby each optimizes quality of and capability for the other. Our sedentary, sleep-restricted lifestyle conflicts with our genotype to generate pathophysiologic phenotypes, especially obesity. Insufficient sleep is pandemic, and other sleep disorders are increasingly common. Sleep dysfunction promotes obesity due to inactivity from sleepiness and to metabolic changes. Obesity is the primary risk factor for obstructive sleep apnea, which commonly disrupts sleep. This represents one of many pathophysiologic vicious cycles involving inactivity, sleep disorders, and obesity. Solutions include better education of the medical community, which remains surprisingly ignorant about these disease processes and therapeutic advantages of exercise and sleep repletion. Doctors commonly prescribe medications with sleep disruption or weight-gain side effects instead of lifestyle modifications. Lifestyle improvements often provide superior treatment to medications and impose no side effects.