This perspective article reviews the design and application of covalent organic frameworks (COFs) as single-site photocatalysts (SSPCs) for solar-to-fuel conversion. COFs, with their high surface areas, structural diversity, and chemical stability, are attractive candidates for SSPCs due to their molecular-level precision and intrinsic light-harvesting ability. The authors summarize the design concepts and strategies for constructing COF SSPCs, highlighting their applications in photocatalytic water splitting and CO2 reduction. They discuss the importance of thermodynamic and kinetic factors in achieving efficient solar-to-fuel conversion and the role of single-site catalysts in enhancing catalytic efficiency. The article also addresses the challenges and future directions in the field, emphasizing the need for standardized evaluation systems, detailed characterizations of single-site catalysts, and the development of stable and scalable COF SSPCs.This perspective article reviews the design and application of covalent organic frameworks (COFs) as single-site photocatalysts (SSPCs) for solar-to-fuel conversion. COFs, with their high surface areas, structural diversity, and chemical stability, are attractive candidates for SSPCs due to their molecular-level precision and intrinsic light-harvesting ability. The authors summarize the design concepts and strategies for constructing COF SSPCs, highlighting their applications in photocatalytic water splitting and CO2 reduction. They discuss the importance of thermodynamic and kinetic factors in achieving efficient solar-to-fuel conversion and the role of single-site catalysts in enhancing catalytic efficiency. The article also addresses the challenges and future directions in the field, emphasizing the need for standardized evaluation systems, detailed characterizations of single-site catalysts, and the development of stable and scalable COF SSPCs.