Organic chemistry is in the unique position to provide molecular level insights into biological processes. Renewed appreciation for the power of small molecules as tools to explore living systems has fueled an explosion of interest in chemical biology. Within this broad context, our research program is focused on the development of new synthetic methodology to expedite the discovery of biologically active molecules. We are strategically combining elements of microwave-assisted organic chemistry, solid-phase synthesis, and combinatorial chemistry to provide access to new classes of chemical probes. In turn, we are applying these small molecule tools to bacterial communication and host/microbe interactions, previously unexamined areas of chemical biology. We seek to understand how both plants and animals sense and respond to invasion by pathogenic microbes. The ability of bacteria to communicate with each other and function as a group is a critical step in the development of infectious disease. The reliance of bacteria on a language of small molecules places organic chemists in a unique position to discover the fundamental principles underlying this communication network and design tools to modulate it at the molecular level.