Abstract: Historically tools and technologies facilitated scientific discoveries. Steroid hormone research is not an exception. Unfortunately, the dramatic advancement of the field faded this research area and flagged it as a solved topic. However, it should have been the opposite. The area should glitter with its strong foundation and attract next-generation scientists. Over the past century, a myriad of new facts on biochemistry, molecular biology, cell biology, physiology and pathology of the steroid hormones was discovered. Several innovations were made and translated into life-saving treatment strategies such as synthetic steroids, and inhibitors of steroidogenesis and steroid signaling. Steroid molecules exhibit their diverse effects on cell metabolism, salt and water balance, development and function of the reproductive system, pregnancy, and immune-cell function. Despite vigorous research, the molecular basis of the immunomodulatory effect of steroids is still mysterious. The recent excitement on local extra-glandular steroidogenesis in regulating inflammation and immunity is revitalizing the topic with a new perspective. Therefore, here we review the role of steroidogenesis in regulating inflammation and immunity, discuss the unresolved questions, and how this area can bring another golden age of steroid hormone research with the development of new tools and technologies and advancement of the scientific methods.