Rechargeable aqueous manganese-based batteries have been attracting significant attention owing to their advantages of low cost, high safety, and ease of manufacturing, which are promising attributes for grid-scale energy storage applications. However, most traditional manganese-based batteries with solid-state conversion and intercalation reactions suffer from low capacity and poor long-term cycling stability. The recent novel storage mechanism based on cathode Mn2+/MnO2 deposition/stripping chemistry has fundamentally tackled these issues, enabling a new generation of manganese-based batteries with superior electrochemical performance. Here, the recent advances in aqueous manganese-based batteries with the Mn2+/MnO2 deposition/stripping chemistry are reviewed. A summary of the development of manganese-based batteries with different storage mechanisms is provided and new opportunities for the emerging Mn2+/MnO2 chemistry in the latest generation are highlighted. Then, the current understanding of the Mn2+/MnO2 charge storage mechanism and its potential in manganese-based batteries for large-scale energy storage applications is presented. Moreover, insights into opportunities and future directions for manganese-based batteries with the Mn2+/MnO2 chemistry are proposed.