The ready availability of structurally novel lead molecules with appropriately controlled molecular properties (e.g. logP, molecular weight and fraction of sp3 atoms) is crucial to the ability of the pharmaceutical industry to bring new small molecule drugs to market. However, it is now recognised that access to such lead molecules is poorly served not only by many current commercial libraries but also by the synthetic methods widely adopted within industry and many of those developed in academic laboratories. In this meeting, approaches to rectifying this issue will be presented both from academia and industry, with the hope of stimulating a broader recognition of, and solutions to, the challenges of lead-oriented synthesis.