Metal single-atom catalysts (SACs) play an essential role in small molecule related energy conversion. Metal-organic frameworks (MOFs), which contain the highly ordered arrays of organic linkers and metal nodes, as well as the clearly defined pore structures, are considered as an ideal platform to fabricate atomically dispersed metal sites. In this review, we summarize the approaches for fabricating MOF-based SACs by utilizing their structure characteristics. A brief discussion is also given about the feasible techniques to characterize SACs. A series of representative examples of MOF-based SACs and their energy-related applications, mainly in photocatalysis and electrocatalysis, are discussed. The challenges and future development opportunities of MOF-based SACs are highlighted.