Family 3 carbohydrate-binding modules (CBM3s) are among the most distinctive, diverse, and robust. CBM3s, which are numerous components of both free cellulases and cellulosomes, bind tightly to crystalline cellulose, and thus play a key role in cellulose degradation through their substrate targeting capacity. In addition to the accepted cellulose binding surface of the CBM3 molecule, a second type of conserved face (the "shallow groove") is retained on the opposite side of the molecule in all CBM3 subfamilies, irrespective of the loss or modification of the cellulose-binding function. The exact function of this highly conserved shallow groove is currently unknown. The cellulosomal system contains many linker segments that interconnect the various modules in long polypeptides chains. These linkers are varied in length (5-700 residues). The long linkers are commonly composed of repeated sequences that are often rich in Ser, Pro, and Thr residues. The exact function of the linker segments in the cellulosomal system is currently unknown, although they likely play several roles. In this chapter, we document the binding interaction between the conserved shallow-groove region of the CBM3s with selected cellulosomal linker segments, which may thus induce conformational changes in the quaternary structure of the cellulosome. These conformational changes would presumably promote changes in the overall arrangement of the cellulosomal enzymes, which would in turn serve to enhance cellulosome efficiency and degradation of recalcitrant polysaccharide substrates. Here, we describe two different methods for determining the interactions between a model CBM3 and cellulosomal linker peptides.