Chemistry has long been an integral part of toxicology, as the two fields originated in much the same way: the investigation of plants with interesting properties. In this chapter I review the role that chemistry has played in understanding toxic and medicinal plants. After some introductory remarks, three broad areas are addressed: the role of natural products in understanding plant taxonomy and evolution, recent developments in chemical synthesis, especially efforts to discover and efficiently synthesize novel structures based upon naturally occurring toxins, and finally, developments in the new field of systems toxicology, which seeks to integrate all aspects of an organism's response to toxic insult.