Hormone secretion from endocrine glands constitutes a primary component of homeostatic control systems that defend whole body tissue viability and function. Endocrine organ secretion is controlled by efferent mechanisms that consist of both hormonal and neural elements. Anatomical evidence for dual control has led to increased understanding of how autonomic neural activity modulates functional sensitivity to hormonal input. The clinical relevance of autonomic-endocrine interactions is illustrated by examining functional control of the adrenal cortex and the ovary, two tissues that require tropic support from the anterior pituitary and receive sympathetic neural input. Extrapituitary mechanisms of adrenal cortical control including sympathetic neural activity have been implicated in controlling the amplitude of the cortisol awakening response (CAR), a diagnostic index of hypothalamic-pituitary-adrenal activity in humans. In addition, increases in sympathetic neural tone have been implicated in polycystic ovary syndrome (PCOS), a leading cause of female infertility. These examples offer strong evidence for the capability of autonomic neural activity to alter the functional sensitivity of endocrine glands. This interaction has significant clinical relevance and needs to be incorporated into our view in assessing endocrine organ function and dysfunction.