Covalent organic frameworks (COFs) are emerging as promising single-site photocatalysts for solar-to-fuel conversion. Unlike traditional inorganic materials, COFs offer high surface areas, structural diversity, and chemical stability, making them ideal for single-site photocatalysts (SSPCs). This Perspective summarizes the design concepts and strategies for constructing COF SSPCs, their development, and applications in solar-to-fuel conversion. It also discusses challenges in photocatalytic characterization and future directions for this field. SSPCs are defined by well-defined, spatially separated active sites with identical interaction energies with reactants. COFs, with their high porosity and surface area, are particularly suitable for SSPCs, as they can enhance the utilization of photogenerated charges. COF SSPCs can be categorized into three main types: non-bonded, covalently tethered, and metalated. Each category has distinct electron transfer mechanisms, with non-bonded and covalently tethered COF SSPCs primarily relying on outer-sphere electron transfer, while metalated COF SSPCs use inner-sphere electron transfer. COF SSPCs have been successfully applied in solar-driven water splitting and CO₂ reduction. For example, cobaloxime-based COF SSPCs have demonstrated high hydrogen evolution rates and selectivity. Similarly, Re-based COF SSPCs have shown efficient CO₂ reduction with high selectivity and stability. These systems highlight the potential of COFs in achieving high photocatalytic efficiency and stability. Despite these advancements, challenges remain, including the need for standardized evaluation systems to compare photocatalytic activities across different studies. Additionally, the long-term stability and scalability of COF SSPCs are critical factors for practical applications. Efforts are ongoing to develop COF SSPCs that operate in aqueous media and use earth-abundant elements to enhance sustainability. In conclusion, COF SSPCs represent a promising avenue for solar-to-fuel conversion, with ongoing research aimed at improving their efficiency, stability, and scalability. Future directions include optimizing photocatalytic operation conditions, understanding the catalytic mechanisms, and developing COF SSPCs that can operate in aqueous environments without sacrificial agents. These advancements will be crucial for the practical implementation of COF SSPCs in renewable energy technologies.Covalent organic frameworks (COFs) are emerging as promising single-site photocatalysts for solar-to-fuel conversion. Unlike traditional inorganic materials, COFs offer high surface areas, structural diversity, and chemical stability, making them ideal for single-site photocatalysts (SSPCs). This Perspective summarizes the design concepts and strategies for constructing COF SSPCs, their development, and applications in solar-to-fuel conversion. It also discusses challenges in photocatalytic characterization and future directions for this field. SSPCs are defined by well-defined, spatially separated active sites with identical interaction energies with reactants. COFs, with their high porosity and surface area, are particularly suitable for SSPCs, as they can enhance the utilization of photogenerated charges. COF SSPCs can be categorized into three main types: non-bonded, covalently tethered, and metalated. Each category has distinct electron transfer mechanisms, with non-bonded and covalently tethered COF SSPCs primarily relying on outer-sphere electron transfer, while metalated COF SSPCs use inner-sphere electron transfer. COF SSPCs have been successfully applied in solar-driven water splitting and CO₂ reduction. For example, cobaloxime-based COF SSPCs have demonstrated high hydrogen evolution rates and selectivity. Similarly, Re-based COF SSPCs have shown efficient CO₂ reduction with high selectivity and stability. These systems highlight the potential of COFs in achieving high photocatalytic efficiency and stability. Despite these advancements, challenges remain, including the need for standardized evaluation systems to compare photocatalytic activities across different studies. Additionally, the long-term stability and scalability of COF SSPCs are critical factors for practical applications. Efforts are ongoing to develop COF SSPCs that operate in aqueous media and use earth-abundant elements to enhance sustainability. In conclusion, COF SSPCs represent a promising avenue for solar-to-fuel conversion, with ongoing research aimed at improving their efficiency, stability, and scalability. Future directions include optimizing photocatalytic operation conditions, understanding the catalytic mechanisms, and developing COF SSPCs that can operate in aqueous environments without sacrificial agents. These advancements will be crucial for the practical implementation of COF SSPCs in renewable energy technologies.