Small molecules govern many essential processes in the natural world. From interspecies communication to the development and progression of human diseases, determining the roles of small molecules is central to our understanding of these complex systems. The Linington lab is interested in the development of new technologies that accelerate bioactive compound discovery. In this lecture I will present new developments in high-content screening and untargeted metabolomics for natural products discovery, and highlight how my group is using computational methods to integrate these new technologies. The ultimate objective of this study is to create methods for the rapid and accurate characterization of the full chemical landscape of natural products libraries, and to connect this chemical information to biological functions in specific bioassay systems.