The outcome of plant-pathogen interactions is influenced significantly by endogenous small molecules that coordinate plant defence responses. There is currently tremendous scientific and commercial interest in identifying chemicals whose exogenous application activates plant defences and affords protection from pathogen infection. In this review, we provide a survey of compounds known to induce disease resistance in plants, with particular emphasis on how each compound was originally identified, its putative or demonstrated mechanism of defence induction, and the known biological target(s) of each chemical. Larger polymeric structures and peptides/proteins are also discussed in this context. The quest for novel defence-inducing molecules would be aided by the capability for high-throughput analysis of candidate compounds, and we describe some issues associated with the development of these types of screens. Subsequent characterization of hits can be a formidable challenge, especially in terms of identifying chemical targets in plant cells. A variety of powerful molecular tools are available for this characterization, not only to provide insight into methods of plant defence activation, but also to probe fundamental biological processes. Furthermore, these investigations can reveal molecules with significant commercial potential as crop protectants, although a number of factors must be considered for this potential to be realized. By highlighting recent progress in the application of chemical biology techniques for the modulation of plant-pathogen interactions, we provide some perspective on the exciting opportunities for future progress in this field of research.