Cardiovascular function exhibits dramatic fluctuations over the course of a normal day. Upon awaking, parameters such as heart rate and blood pressure rise steeply, and remain elevated throughout the day. Moreover, profound time-of-day-dependent rhythms are observed in cardiovascular-relevant organs (such as the heart) at molecular, biochemical, and histological levels. Classically, time-of-day-dependent fluctuations in cardiovascular parameters have been attributed to behavior-induced perturbations in neurohumoral factors, such as sympathetic tone. However, recent human- and animal- based studies suggest that intrinsic timekeeping mechanisms, known as circadian clocks, contribute towards these daily rhythms. Circadian clocks are cell autonomous molecular mechanisms, consisting of a series of positive and negative feedback loops, with a periodicity of approximately 24-hrs. These clocks confer the selective advantage of anticipation, allowing a cell/organ to prepare for a stimulus/stress prior to its onset. Circadian clocks have been identified in essentially all mammalian cells, including cardiomyocytes. Studies utilizing murine models of cardiomyocyte circadian clock genetic disruption suggest that this mechanism temporally regulates numerous biological processes known to be critical for cardiac function. These include transcription, protein turnover (synthesis and degradation), cellular signaling, electrophysiology, and metabolism. Moreover, the cardiomyocyte circadian clock appears to influence the sensitivity of the heart to both physiologic stimuli (e.g., insulin, fatty acids) and pathologic stresses (e.g., ischemia/reperfusion, pro-hypertrophic stimuli). Chronic disruption of this molecular timekeeper precipitates cardiac dysfunction, including increased cardiomyocyte size (hypertrophy), interstitial fibrosis, and contractile impairments. Interestingly, pharmacological strategies designed to target the circadian clock (e.g., small molecule agonists targeting the clock component REV-ERBa/b) have yielded promising beneficial effects in pre-clinical animal models of cardiac disease (e.g., heart failure). Collectively, these studies highlight the importance of the cardiomyocyte circadian clock in maintenance of normal cardiac physiology, and the potential of targeting this molecular mechanism for the future prevention/treatment of heart diseases.