Abstract : Over the past fifty years our knowledge of the evolution of proteins in living cells has been mapped in terms of molecular architecture and amino acid sequence. Second generation methods of gene sequencing are now allowing us to investigate genetic diseases and follow the emergence of resistance as tumours evolve to escape the restraints of tissue function and as pathogens such as Mycobacterium tuberculosis and HIV evade the immune response of the host. I will discuss work in my laboratory funded by the Wellcome Trust on cancer and genetic diseases such as von Hippel Lindau diseases and alkaptonuria, and by the Gates Foundation on tuberculosis. I will describe both bioinformatics and computational approaches that contribute to a multidisciplinary approach to drug discovery. I will discuss the challenges of making new medicines against emerging resistance in cancer and tuberculosis