Cellulose is a major source of glucose because it is readily available, renewable, and does not compete with the food supply. Hydrolysis of cellulose is experiencing a new research and development cycle in which this reaction is carried out over solid catalysts and coupled to other reactions for increased efficiency. Cellulose is typically not soluble in conventional solvents and very resistant to chemical and biological transformations. This Review focuses on aspects related to the hydrolysis of cellulose as this process is a significant entry point into the biorefinery scheme based on carbohydrates for the production of biofuels and biochemicals. Structural features of cellulose, conventional acid-catalyzed reactions, and the use of solid acid catalysts for hydrolysis are discussed. The longterm success of the biorefinery concept depends on the development of energetically efficient processes to convert cellulose directly or indirectly into biofuels and chemicals.