Streptococcus pneumoniae colonization of the human airway is an essential precursor for disease; however, the mechanisms by which the bacterium establishes and maintains colonization are poorly understood. It is becoming increasingly clear that S. pneumoniae expresses glycosidases that can modify many glycan structures present in the human airway, including N-linked glycans, O-linked glycans, and glycosaminoglycans. Many of these glycosidases have been shown to contribute to in vivo colonization. Although the precise role of these glycosidases during colonization remains to be elucidated, in vitro assays suggest that pneumococcal modification of host sugars may contribute to colonization in a variety of ways. Experimental evidence supports a role for pneumococcal glycosidases in providing a carbon source for growth, biofilm formation, competition with other bacteria within the airway, and exposing receptors for adherence. Herein we review the ability of S. pneumoniae to modify host sugars and the functional effects of these modifications.