The cell’s responsivity to a secretagogue is determined by several factors. This chapter identifies several Adenosine triphosphate (ATP)-consuming steps have now been identified in the sequence of stimulus-secretion coupling in various secretory cells, such as the phosphorylation of phosphatidylinositol and diacylglycerol, adenylate cyclase, protein kinases, and actomyosin ATPase. The high ATP-turnover in resting platelets may therefore be related to the specific functions of these cells, aggregation and secretion of a variety of granule-stored substances. Depletion of cellular ATP leads to reduced insulin binding to rat soleus muscle cells, adipocytes, and hepatocytes, independent of the inhibition of receptor internalization and replenishment. Formation of new filaments from monomelic actin is slow, nucleation being the rate-limiting step, which seems incompatible with the observed rapid changes in cell morphology during secretion responses. The actual sensitivity depends on the properties of the interactions between cycle intermediates and the adjacent components of the particular pathway, which in general will result in a somewhat lower factor.