Hydrogen, the universe’s most elementary element, plays a crucial role in cosmic genesis and the evolution of life. In recent times, the field of hydrogen medicine has experienced rapid advancements, revealing novel trends and challenges. This review delineated significant milestone events in the evolution of hydrogen medicine and sorted out the general trend of its development. It evaluated the present state and emerging trends of hydrogen medicine in terms of therapeutic effects, molecular mechanisms, research domains, and models. The review also provides recommendations for addressing current challenges in hydrogen medicine.