Lignocellulosic biomass (LCB) has remained a latent alternative resource to be the main substitute for oil and its derivatives in a biorefinery concept. However, its complex structure and the underdeveloped technologies for its large-scale processing keep it in a state of constant study trying to establish a consolidated process. In intensive processes, enzymes have been shown to be important molecules for the fractionation and conversion of LCB into biofuels and high-value-added molecules. However, operational challenges must be overcome before enzyme technology can be the main resource for obtaining second-generation sugars. The use of additives is shown to be a suitable strategy to improve the saccharification process. This review describes the mechanisms, roles, and effects of using additives, such as surfactants, biosurfactants, and non-catalytic proteins, separately and integrated into the enzymatic hydrolysis process of lignocellulosic biomass. In doing so, it provides a technical background in which operational biomass processing hurdles such as solids and enzymatic loadings, pretreatment burdens, and the unproductive adsorption phenomenon can be addressed.