The understanding of the endocrine changes in critically ill children is important, as it provides insights in the pathophysiology of the acute stress in children and its differences compared with adults. Furthermore, it delineates prognostic factors for survival and supports the rational use of present and future pharmaceutical interventions. Much more than in critically ill adults, the acute phase of critical illness comes into prominence in critically ill children, as they show a very rapid and fierce course of disease, followed by a quick recovery if they survive. This chapter presents a comprehensive summary of the results of various studies undertaken to evaluate endocrine changes seen during the acute stress response in critically ill children suffering from sepsis or septic shock with purpura (Chapters 2 to 6) or undergoing open-heart surgery (Chapter 7). These studies evaluated three hypothalamic-pituitary-end-organ axes: I. Hypothalamic-pituitary-adrenal axis (Chapter 2 and Chapter 3) II. Hypothalamic-pituitary-thyroid axis (Chapter 4 and Chapter 5) III. Growth hormone / insulin-like growth factor axis (Chapter 6 and Chapter 7) Chapter 1 provides a general overview of these hormonal axes and the current knowledge on the changes during the acute phase of critical illness in children and adults.