T he products of pioneering “split and mix” combinatorial synthesis techniques were multi-component mixtures of products either in solution or tethered to beads which required imaginative screening and deconvolution strategies to return information on the activity of individual components, often present in sub-microgram quantities. In recent years we have witnessed the development of a range of sophisticated synthesisers and other high throughput parallel synthesis techniques capable of delivering large numbers of compounds for screening in quantities from 10 to 50 mg. Such compounds have the potential for purification, characterisation and quantification and hence provide a high quality, long lasting screening resource. This paper will describe processes in place at SmithKline Beecham to ensure that such criteria are met, and will focus primarily on high throughput purification by preparative HPLC.