As scientists and physicians have gained sophistication in understanding and treating illness, our view of disease has changed in scope. We appreciate more fully the diverse and wide-ranging effects of stress on the ability of the organism to maintain homeostasis. As our study of the failure of homeostasis has advanced from the organ to the intracellular level, we have gained insight into processes that, through conveyance of chemical messages, cross organ boundaries to tie together multiple systems involved in preserving metabolic balance. We have come to recognize that our pharmacologic interventions are seldom unique in the sense of providing the patient with an entirely new means of fighting an illness; we more often support a system that has been deranged by disease or injury, using agonists, inhibitors, buffers, substitutes, supplements, and mechanical devices in hopes that the body will adjust to its stresses over time. Multiple receptor systems have been studied in regard to their function in normal and abnormal states. Of primary impact on the critically ill patient are adrenergic, thyroid, and insulin receptors, which are of major importance in maintaining metabolic stability and are either the targets of many of our therapies or are inadvertently affected by them in adverse ways. Of doubtless importance, but currently with less clinical application in this setting, are steroid, cholinergic, and histamine receptors. The recent growth of data concerning the role of endogenous opioids in the response to stress will, it is hoped, add to our armamentarium in the future. Future research in signal transduction will continue to increase our understanding of the mechanisms through which our patients maintain homeostasis in the face of disease, as well as our role in helping to regain a balance that has been lost. With further study, we may develop pharmacologic agents that allow us to effect changes with greater tissue or subcellular specificity and hence more specific physiologic consequences. As in many other fields of medicine, continued description of normal states will aid in recognition of defects in the abnormal, or unregulated, state, by understanding derangements in control that can result in primary disease.