Carbohydrates are the most prominent features of the cell’s exterior—they are the cell’s “face” and serve as the cell’s identification card. The features of cell surface glycans (e.g. glycoproteins, glycolipids, polysaccharides) can be read by proteins, other cells, or organisms. In all of these contexts, glycan-binding proteins typically recognize (“read”) glycan identity. This recognition mediates important host-microbe interactions, as well as critical physiological functions, including fertilization, development, and immune system function. This article focuses on how proteins recognize glycans with an emphasis on three objectives: 1) to understand the molecular basis for carbohydrate recognition, 2) to implement that understanding to develop functional probes of protein-carbohydrate interactions, and 3) to apply those probes to elucidate and exploit the physiological consequences of protein–carbohydrate interactions. In this context, our group has focused on two key aspects of carbohydrate recognition: CH-π and multivalent interactions. We are applying the foundational knowledge gained from our studies for purposes ranging from illuminating host-microbe interactions to probing immune system function.