Chemical similarity between two or more molecules can be calculated using some sort of fingerprints and one of the many similarity indices. This talk will cover use of Daylight fingerprints and Tanimoto similarity index. Ability of Daylight fingerprints to capture structural features of any type of molecule is unique among various molecular descriptors that are commercially available; they do need to be 'calibrated' to gain the maximum information that is present in molecules of different sizes. The two most important parameters that need to be correctly set are size of the fingerprints and the maximum lengths between atom pairs. Application of similarity will be exemplified with clustering algorithm, dbclus, finding close analogues in HTS and from lead molecules, design of training and test sets for QSAR, and potential use in quality control, QC, of experimental data.