The hypothalamic-pituitary-adrenal response to stress is a dynamic process. The homeostatic corrections that have emerged in the course of human evolution to cope with the catastrophic events during critical illness involve a complex multisystem endeavor. Although the repertoire of endocrine changes has been probed in some detail, discerning the vulnerabilities and failures of this system is far more challenging. One of the most controversially debated topics in the current literature is the characterization and optimal treatment of allegedly inadequate adaptations of the hypothalamic-pituitary-adrenal axis during critical illness. This outline attempts to touch briefly some of the debated issues, stir the discussion, and thereby contribute to resolving the dispute.