While a basic assumption in the field of circadian biology is that the health and well being of an organism depends upon the appropriate phase relationship of many diverse internal 24 hour rhythms at the levels of the cell, tissue, organ, as well as the whole organism, there has been remarkably little evidence from animal studies that disrupting normal circadian organization, or in fact abolishing circadian rhythmicity, is actually "bad" for the health of the organism. Martino, et al. demonstrate in this issue of the AJP that severe cardiovascular and renal disease are observed in a hamster carrying a mutation that alters the intrinsic circadian period; however, this only happens when the animals are entrained to a light-dark cycle that creates disorganization within the circadian system, and does not occur if the mutant animals are entrained to an LD cycle similar to their mutant intrinsic circadian period, or if they are rendered "rhythmless" due to abolition of the central circadian clock in the SCN. These results, as well as other recent findings, suggest that we will need to exploit many different genetic and non-genetic animal models under a range of environmental conditions in order to elucidate the extent to which circadian disruption leads to tissue specific as well as global disease states, particularly for age-related mental and physical diseases, before we understand how disrupted rhythms, as well as perhaps no rhythms at all, impact the health and well being of the organism.