The QSAR paradigm is delineated as it evolved and as it is presently used. The methodology used to select appropriate substituents/compounds, parameters, and approaches is addressed. Parameters that are routinely used to define a QSAR are sequestered according to their electronic, hydrophobic, and steric attributes. Indicator variables and molecular structure descriptors are also described. The types of QSAR models that are featured include the linear and parabolic models elucidated by Hansch and the bilinear model developed by Kubinyi. Applications of QSAR are drawn from isolated receptor systems as well as cellular and whole animal studies. The utility of a comprehensive QSAR database that allows for lateral validation from physical organic reactions and other biological systems is described and illustrated.