Living systems developed cellular clocks to synchronize and optimize energetic processes controlling metabolism, restorative processes such as sleep, and reproductive processes, which have a metabolic cost (but are necessary for survival) to nutrient cycles that follow an environmental 24-h rhythm. Sleep is highly organized and influences health and longevity through endocrine and metabolic systems, including the hypothalamic-pituitary-testicular axis, which governs puberty, androgenization, and male fertility through Leydig cell synthesis of testosterone, the male hormone and the main anabolic signal in men. The Leydig cell contains a functional cellular clock that is synchronized by cortisol as the main central timing signal of the central circadian pacemaker. Cortisol is also the main central timing signal for metabolically important organs and is the major catabolic signal. Sleep loss alters cortisol and testosterone toward a catabolic signaling state. These hormonal changes are largely responsible for the induction of insulin resistance from acute sleep loss and presumptively for the development of type 2 diabetes mellitus and other metabolic disorders from chronic sleep loss. The reduction in morning, afternoon, and 24-h testosterone by sleep loss is associated with reduced morning LH. Circadian misalignment, in the absence of sleep loss, has little effect on testosterone. Unlike cortisol, the 24-h rhythm in testosterone is not due to the central circadian pacemaker but is instead a consequence of sleep. This requires consideration for the laboratory evaluation of male hypogonadism in night shift workers, who are more likely than non-shift workers to have symptoms that trigger such an evaluation.