During 1912 to 1941, endocrinology coalesced around the neuroendocrine control of physiology, with the hypothalamus emerging as a central regulator of pituitary function and hormones mediating systemic processes such as metabolism, reproduction, and water balance. Studies highlighted the posterior pituitary’s active principles vasopressin and oxytocin and established prolactin as a distinctive anterior pituitary hormone, signaling the dawn of hormone-specific assays and targeted physiology. A unifying theme was the integration of developmental and cellular polarity concepts—linking structure, secretion, and systemic response across organs such as the thyroid, pancreas, and gonadal axis. Neuroendocrine coordination also framed central control, temperature regulation, and pituitary neural interfaces as foundational to endocrine physiology. Historical Significance: These breakthroughs laid the foundation for modern endocrinology by articulating explicit hormonal pathways governing metabolism, growth, reproduction, and homeostasis. The identification of circulating hormones, the demonstration of endocrine coordination across tissues, and the establishment of hypothalamic–pituitary axes created a durable framework for later discoveries in hormone action, regulation, and therapeutic potential.