Biofuel production from biomass can be divided into four major steps - biomass generation, pretreatment to recover cellulose, cellulose hydrolysis to simpler sugars like glucose, and production from glucose. Enzymatic hydrolysis of cellulose, which is the rate-limiting step in the process, is catalyzed by glycosyl hydrolases. Within the glycosyl hydrolase family of enzymes, cellulases catalyze the breakdown of the β-1,4- linkage in cellulose to smaller oligosaccharides and can be broadly classified into two groups - endo-glucanases and exo-glucanases.  These enzymes are found to be modular in architecture where catalytic domain (CD) that hydrolyzes the glycosidic linkage are sometimes found ‘joined’ together with other accessory non-catalytic domains like carbohydrate binding modules (CBMs) through a flexible linker sequence. While CD hydrolyzes the glycosidic bond, the primary function of the CBMs is binding to the crystalline or amorphous cellulose as an accessory module; CBMs thus present a model system for understanding the structure-function relationship of not only the CBM with cellulose but also for interactions of the CBM with the catalytic domain. The relationship between CBM structure, CBM binding affinity, and optimal enzyme catalytic efficiency had not previously been well-explored although it will play a key role in achieving the cost-effective breakdown of the cellulose in pretreated biomass.  To fill this knowledge gap, we have developed analytical methods to characterize a large set of CBMs from thermophilic cellulolytic enzymes.  The properties of these binding modules will be discussed, with an emphasis on their varying affinities for insoluble cellulosic substrates and how this affects catalytic activities.