The history of adrenal hormones provides a fascinating insight into how the discovery of adrenal hormones transformed our understanding of homeostasis. Owing to the small size of the gland and its anatomical location, there was quite a disparity in its existence for a large part of the time. However, at the dawn of the 19th century, the discovery of microscopes paved the way to identify the glands. In a nutshell, the discovery of various hormones from the adrenal cortex and medulla has been revolutionary both in the understanding of normal physiological processes and their therapeutic uses. A review of existing literature from PubMed eventually carved this article in which evolution in the discovery of these hormones and major clinical aspects related to adrenal hormones is discussed. As always, each discovery found birth in someone's question and was eventually fully realized by cooperative teamwork and leadership. The mechanism of hormones’ action was identified through animal and human experimentation, while scientists demonstrated the structure of hormones using the conventional biochemical analysis. Mostly, diseases were identified as syndromes earlier than hormones.