Metabolic disorders and endocrine changes are common and relevant in critically ill patients. Thereby, endocrinopathies, electrolyte or metabolic derangements may either pre-exist or develop, and left unattended, may lead to significant morbidity and mortality. The homeostatic corrections which have emerged in the course of human evolution to cope with the catastrophic events during critical illness involve a complex multisystem endeavour, of which the endocrine contribution is an integral component. Although the repertoire of endocrine changes has been probed in some detail, discerning the vulnerabilities and failures of this system is far more challenging. The ensuing endocrine topics illustrate some of the current issues reflecting attempts to gain an improved insight and clinical outcome for critical illness. Disturbances in glucose and cortisol homeostasis during critical illness are two controversially debated topics in the current literature. The term “hormokine” encompasses the cytokine like behaviour of hormones during inflammation and infections. The concept is based on an ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide su-perfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Procalcitonin is the protopye of “hormokine” mediators circulating procalcitonin levels increase several 10 000-fold during sepsis improve the clinical assessment especially of respiratory tract infections and sepsis safely and markedly reduces antibiotic usage in non-bacterial respiratory tract infections and meningitis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Hormokines are not only biomarkers of infection. Hormokines are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. Yet, with increasing levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralization of hormokines during infection was shown to improve survival and thus might open new treatment options for severe infections, especially of the respiratory tract.