A crucial component of the application of quantitative methods to drug design is the characterisation of chemical structures using measured or calculated physicochemical descriptors. Over the course of the last 50 years or so, this topic has grown in complexity from a small set of a few tens of different properties to thousands of possible parameters. Despite this phenomenal growth, there is still no accepted set of universally applicable descriptors. This chapter describes the development of several different classes of physicochemical properties, discussing some of the problems involved in their interpretation.