Altering timing perturbs cell signaling Biological regulatory systems have been optimized by evolution to accommodate environmental variation. Yet these systems may also have fragile aspects that can be exposed by variation in the timing of signaling events. Mitchell et al. studied the properties of the yeast signaling system that allows cells to adapt to changing osmotic conditions. The same properties also made the system sensitive to hyperactivation and the consequent inhibition of cell growth if exposed to oscillations in osmotic conditions with a particular frequency. The identification of similar fragility in other regulatory pathways might prove useful in the development of therapeutic strategies against diseases in which signaling is perturbed, such as cancer and diabetes. Science , this issue p. 1379