We tend to think of metabolites as simple building blocks and fuel for biological processes. But many metabolites appear to play crucial roles in regulating living systems. This concept of metabolite signaling remains poorly understood at the biochemical level, and we still do not understand how most metabolite signals work. Edward Chouchani’s lab is developing new technologies to better understand the rules of the language of core metabolite signals. The hope is that by understanding how nature uses metabolism to regulate biological systems, we will have new opportunities for treating human disease.