The article reviews the factors that limit the complete hydrolysis of lignocellulosic substrates by microbial enzymes. Despite extensive research, the mechanisms of cellulose degradation remain complex and multifaceted. The efficacy of enzymatic complexes in hydrolyzing these substrates is closely linked to the structural characteristics of the substrate and the modifications that occur during saccharification. Key substrate characteristics include degree of polymerization, crystallinity, accessible surface area, particle size, and lignin distribution. Enzyme factors such as synergism and adsorption also play crucial roles. Synergism, where the combined action of multiple enzymes exceeds the sum of their individual actions, is particularly important for efficient hydrolysis. Adsorption, facilitated by cellulose-binding domains (CBDs), is essential for enzyme-substrate interaction, with CBDs increasing enzyme concentration at the substrate surface and enhancing adsorption. The article highlights the challenges in understanding the interactions between enzymes and substrates, especially in natural lignocellulosic materials, and emphasizes the need for further research to fully elucidate the mechanisms of cellulose hydrolysis.The article reviews the factors that limit the complete hydrolysis of lignocellulosic substrates by microbial enzymes. Despite extensive research, the mechanisms of cellulose degradation remain complex and multifaceted. The efficacy of enzymatic complexes in hydrolyzing these substrates is closely linked to the structural characteristics of the substrate and the modifications that occur during saccharification. Key substrate characteristics include degree of polymerization, crystallinity, accessible surface area, particle size, and lignin distribution. Enzyme factors such as synergism and adsorption also play crucial roles. Synergism, where the combined action of multiple enzymes exceeds the sum of their individual actions, is particularly important for efficient hydrolysis. Adsorption, facilitated by cellulose-binding domains (CBDs), is essential for enzyme-substrate interaction, with CBDs increasing enzyme concentration at the substrate surface and enhancing adsorption. The article highlights the challenges in understanding the interactions between enzymes and substrates, especially in natural lignocellulosic materials, and emphasizes the need for further research to fully elucidate the mechanisms of cellulose hydrolysis.