The CFEM (Common in Fungi Extracellular Membrane) proteins are cell membrane proteins exclusive to fungi, playing a crucial role in fungal growth, development, pathogenicity, and host interactions. This article elaborates on the structure, origin, evolution, functions, and molecular mechanisms of CFEM proteins in various pathogenic fungi. CFEM proteins exhibit a dispersed distribution in fungi, with a higher prevalence in pathogenic species. They play significant roles in maintaining iron balance, cell wall integrity, and the infection process. The discussion and outlook focus on future research regarding the role and molecular mechanism of CFEM proteins in pathogenic infection. Simultaneously, the current research status and challenges of CFEM are discussed, offering insights into the understanding of the interactions between microorganisms and plants, as well as providing reference points for strategies in microbial-plant interactions and control measures.