When disease or trauma progresses to a critical state, the reaction of the endocrine system in creating homeostasis is essential for survival. The association between the severity of hormonal changes and outcome in terms of morbidity and mortality has led to the challenge of development of several endocrine treatments. During sepsis, nitric oxide-mediated apoptosis is observed in the neurons and glial cells of the cerebrovascular centers of the autonomic nervous system. It is probably one of the components of the circulatory dysfunction of sepsis. The regulation of different organs was neither linear nor independent however organs were found to behave as biological oscillators coupled to each other through neurological or hormonal communication pathways. Sepsis, because of systemic inflammatory responsive syndrome, disrupts these communication pathways and leads to organ failures. Endocrine hormonal issues related to the intensive care setting are common challenges to ICU specialists. Disruptions of the endocrine system in sepsis are characterized by 1) an increase in cortisol plasma levels with a loss of the circadian rhythm of its secretion; 2) hyperglycemia due to insulin resistance and rise in hyperglycemic hormones secretion; 3) relative vasopressin deficiency; and 4) euthyroid sick syndrome or non-thyroidal illness syndrome. This article discusses the dynamic changes of four main endocrine axes: hypothalamic-pituitary-adrenal axis, insulin, vasopressin and thyroid during grave states of disease, when a patient is in critical condition.