Drug discovery is a process by which a novel biological concept is translated into clinical applications. During the process, chemistry plays critical roles not only in generating effective therapeutic modalities but also in understanding the biology and its translation at the molecular level. In this talk, genesis and evolution of drug discovery process will be outlined and the essence of modern drug discovery described, followed by a few case examples where ‘translational chemistry’ is highlighted as a key component in such a multidisciplinary endeavor as drug discovery.