Circadian rhythmicity can be important in the pathophysiology, diagnosis, and treatment of clinical disease. Due to the difficulties in conducting the necessary experimental work, it remains unknown whether ~24-h changes in pathophysiology or symptoms of many diseases are causally linked to endogenous circadian rhythms or to other diurnal factors that change across the day, such as changes in posture, activity, sleep or wake state, or metabolic changes associated with feeding or fasting. Until the physiology is accurately known, appropriate treatment cannot be designed. This review includes an overview of clinical disorders that are caused or affected by circadian or diurnal rhythms. The clinical side effects of disruption of circadian rhythmicity, such as in shiftwork, including the public health implications of the disrupted alertness and performance, are also discussed.