As the interface between the fungal cell and its surroundings, the fungal cell wall (FCW) plays an essential physiological role in a myriad of biological processes. It provides support, protection, and enables material exchange with the environment, playing a key role in microbiome and host–microbe interactions. The fact that FCWs are mainly composed of complex carbohydrates makes carbohydrate-active enzymes (CAZymes) the main players in FCW remodelling and degradation. Despite the biological importance of these processes, our understanding of the underlying enzymology remains limited. In this review, we discuss the role of FCW-active CAZymes in various contexts, including fungal physiology, pathogenesis, human gut microbiomes, and the global carbon cycle, while highlighting knowledge gaps and potential applications in agriculture, biotechnology, and health.