In recent years, there has been a significant increase in the studies on effective energy-conversion devices, including photovoltaics and fuel cells, which aim to alleviate the enormous energy demand, as well as the environmental pollution issues associated with current power consumption. Among these devices, dye-sensitized solar cells (DSCs) have received significant attention owing to their simple fabrication procedure, cost-effectiveness and high-power-conversion efficiency. The counter electrode (CE) of the DSCs is an important component and generally uses platinum as its benchmark material, the high cost and scarcity of which have limited the broad application of the DSCs. Thus, substantial effort has been devoted to seek active CE materials with low cost, high electrocatalytic activity and excellent stability. Nevertheless, this is generally achieved via a ‘trial-and-error’ method owing to the lack of information on the mechanism of the electrocatalytic reaction on the CE’s surface. This report summarizes the recent advances in the mechanistic study of the interfacial electrocatalytic reaction on CE materials, as well as the establishment of a rational screening protocol for efficient CE materials. Furthermore, several outstanding CE materials developed via this protocol have been reviewed. The demonstrated combined approach can be extended to the studies of other essential electrocatalytic reactions. A rational protocol for finding suitable materials for efficient counter electrodes of dye-sensitized solar cells is reviewed. Researchers are actively seeking cheaper alternatives to platinum for counter electrodes, a critical component of dye-sensitized solar cells, but have tended to employ uninformed ‘trial and error’ approaches. Huijun Zhao and co-workers at Griffith University in Australia and the East China University of Science and Technology review recent progress in the development of a rational screening strategy for identifying promising materials for counter electrodes. The strategy employs a combined approach involving theoretical calculations and mechanistic studies. The researchers describe some materials that have been developed using the protocol. They note that the approach can be extended to other electrocatalytic reactions. Finally, future challenges and opportunities in this area are mentioned. This review highlights the recent advances in utilizing a combinatorial strategy of mechanistic investigation, theoretical prediction and experimental validation to develop cheap and earth-abundant high-performance electrocatalysts as counter electrode materials for dye-sensitized solar cells. The effectiveness of the combinatorial strategy over the conventional ‘trial-and-error’ tactic is illustrated with plentiful successful examples of earth-abundant materials. Perspectives are given to elucidate the opportunities and challenges.