The existence of an immune-endocrine interaction has been demonstrated decades ago. An immunomodulatory effect was reported for a wide range of hormones. The best known example for this interaction is the glucocorticoids released by the adrenal cortex. Apart of the glucocorticoids several hormones and neurotransmitters released by these systems are capable of altering immune functions. This includes the catecholamines epinephrine, norepinephrine and dopamine, the pituitary hormone prolactin, and the adrenal hormone dehydroepiandrosterone (DHEA). Several pathological states are paralleled by an activation of the endocrine system leading to an increased hormone release. In line with this an elevated release of catecholamines, of prolactin, and of DHEA has been demonstrated after major surgery, during systemic inflammation and following trauma hemorrhage. Furthermore, due to their pharmacologic properties several neurotransmitters are used as pharmaceutical agents to stabilize cardiovascular function or to prevent organ failure (e.g. epinephrine, norepinephrine, dopamine). Several pharmacological substances interact with the release of immunomodulatory hormones (e.g. metoclopramid and prolactin, dopamine and prolactin) and some hormones are available as over-the counter self medications like DHEA. Therefore, alterations of the serum concentrations of these hormones may affect the immunocompetence of the organism and may thereby affect the clinical course of critically ill patients. The clinical and pharmacological implications of this complex relationship between the endocrine and the immune system will be provided on the background of a review of the recent literature and of our research work.