The methods typically used for studying glucose metabolism in living systems, such as positron-emission tomography (PET) and fluorescence imaging, have drawbacks. PET is expensive and requires radioactive reagents with short half-lives. Fluorescence methods can suffer from high background and low tissue penetration. And glucose labeled with some near-infrared-active fluorophores doesn’t interact properly with the glucose transporter. Elena Goun of the Swiss Federal Institute of Technology, Lausanne (EPFL), and coworkers have developed a pair of reagents—a caged luciferin triphenylphosphine and an azido-modified glucose—that let them use bioluminescence to follow glucose flux (Nat. Methods 2019, DOI: 10.1038/s41592-019-0421-z). When the two reagents are close enough inside a cell, they undergo a reaction that uncages the luciferin. The free luciferin is acted on by the enzyme luciferase, which the researchers engineer into cells or mice. The enzymatic reaction generates light, the intensity of which is proportional to the amount of azido-glucose absorbed. The researchers used the reagents to assess the effects of glucose transport inhibitors on glucose flux in healthy and tumor-bearing mice that had been engineered to produce luciferase. The probe is quantifiable and achieves results comparable to those of PET. Goun believes that the reagents will become powerful tools for drug discovery in cancer metabolism and diabetes. She wants to develop similar reagents for other metabolites.