In terms of sustainable development and environmental issues, the design and fabrication of efficient energy storage devices will be more critical in the future than at any time in the past. Li-S batteries are promising candidates for such a purpose due to their high specific capacity and low environmental impact. This review has systematically retraced the advances in the field of Li-S batteries over the past half century and highlighted the main breakthroughs in a number of areas, covering the mechanism determination, cathode engineering, theoretical simulation, and electrolyte tailoring and anode protection. Furthermore, we discuss the remaining challenges towards their practical application. It is expected that Li-S batteries with 3D inter-connected or conformal assemblies will surpass new horizons in the coming years.