Time-dependent variations in the hormonal and metabolic responses to food are of importance to human health, as postprandial metabolic responses have been implicated as risk factors in a number of major diseases, including cardiovascular disease. Early work reported decreasing glucose tolerance in the evening and at night with evidence for insulin resistance at night. Subsequently an endogenous circadian component, assessed in constant routine (CR), as well as an influence of sleep time, was described for glucose and insulin. Plasma triacylglycerol (TAG), the major lipid component of dietary fat circulating after a meal, also appears to be influenced by both the circadian clock and sleep time with higher levels during biological night (defined as the time between the onset and offset of melatonin secretion) despite identical hourly nutrient intake. These time-dependent differences in postprandial responses have implications for shiftworkers. In the case of an unadapted night shift worker, meals during work time will be taken during biological night. In simulated night shift conditions the TAG response to a standard meal, preceded by either a low-fat or a high-fat premeal, was higher after a nighttime meal than during a daytime meal, and the day/night difference was larger in men than in women. In real night shift workers in Antarctica, insulin, glucose, and TAG all showed an increased response after a nighttime meal (second day of night shift) compared to a daytime meal. Night shift workers are reported to have an approximately 1.5 times higher incidence of heart disease risk and also demonstrate higher TAG levels compared with matched dayworkers. As both insulin resistance and elevated circulating TAG are independent risk factors for heart disease, it is possible that meals at night may contribute to this risk.