The antigen combining site of antibody molecules consists of six separate loops supported by a conserved β-sheet framework. The specificity of the antibody is conferred by the structure of these loops, which in turn is related to their length and sequence variation in both the loops and the supporting framework. This review summarizes the various approaches to modeling the structure of these loops based on homology of the sequence with known crystal structures. For each of the techniques, we discuss the basic methodology, their application, and, where possible, the correlation with experimentally derived structures. The techniques all rely on searching for sequence similarity of various kinds, with the most successful based on the observation that there appears to be a small repertoire of main-chain conformations (or canonical structures) for at least five of the six hypervariable loops and that the particular conformation adopted is determined by a few key conserved residues.