There remains considerable pressure on the pharmaceutical industry to increase productivity and reduce the attrition of drug candidates. Genomics, parallel chemistry and high-throughput biology have not yielded the anticipated benefits, resulting in a renewed focus on validated targets and an aim to generate drugs directed towards such targets, which have a clear advantage. One strategy to identify and develop best-in-class drugs is to apply a high degree of innovation in chemistry and apply this to targets from gene families that have been clinically validated as tractable and drugable. The application of organosilicon medicinal chemistry in the context of privileged structures to aid drug design and development is one such innovative approach that is reviewed in this paper.