Lignocellulosic building blocks are naturally evolved to block their microbial and enzymatic deconstruction. This collective resistance is defined as biomass recalcitrance. It is a result of a sophisticated combination of the crystalline cellulose in microfibrils, heteropolysaccharides, and lignin. This combination is varied in different types of lignocelluloses, various compartment of the cell wall, different ages of the plants, and is also affected by the natural and processing phenomena, such as drying and heating. It is therefore important to understand these factors in order to have effective pretreatment and digestion. This chapter presents a brief overview on the plant cell wall in molecular level and the interaction between the molecules that make the lignocelluloses recalcitrance. In addition, some pretreatments are briefly considered, with the perspective of their effectiveness in reducing the biomass recalcitrance.