The circadian clock coordinates daily physiological, metabolic and behavioral rhythms. In mammals, the suprachiasmatic nucleus (SCN) has been identified as the master circadian clock. The SCN orchestrates circadian rhythms in peripheral tissues and, thereby, generate a synchronized circadian output in physiology and behavior. Little is known about the mechanisms that determine this hierarchy and the central role played by the SCN. In the first part of this talk, I will present our collaborative endeavors to integrate mathematical modeling with single-cell live recordings to gain new insight and quantitatively predictive understanding of the properties that determine the observed hierarchy. In the second part of my talk I will focus on the heterogeneous responses of cancer cells to chemotherapy. In particular, I will show how non-genetic sources of heterogeneity can lead to large cell-to-cell response variability. Our results show how two intertwined cellular features present in every cell have distinct control of cell fate choices in response to the chemotherapeutic drug cisplatin. Contrary to tumor observations, we find that in dividing cells higher proliferation activity increases resistance and that cell cycle state determines the arrest likelihood of the surviving population. These findings show how cellular states shape the individual cell choices that collectively determine the overall response to therapy.