The chemical similarity of compounds can be based on molecular structure or any measured or predicted properties of the molecules, or a combination of the two. The most common approach is to use the molecular structure to assess the chemical similarity within a set of compounds. This approach defines the similarity in terms of the patterns of atoms present in the structures. The patterns of atoms along ‘paths’ through the 2D chemical structure are encoded in a binary ‘fingerprint’ and the similarity of two compounds defined in terms of the Tanimoto index. The advantage of a path-based fingerprint approach to similarity and diversity is that it provides a ‘generic’ method of comparing compounds. No assumption is made regarding the characteristics of molecules that will correlate most strongly with the biological activities of interest. Also, similarity assessed in this way usually corresponds well to a chemist’s view; compounds from within a chemical series will typically have a high Tanimoto index.