Histidine kinases (HKs), together with their partner proteins, the response regulators (RRs), form the ubiquitous two-component systems that are global players in control and adjustment of microbial lifestyle. Although their basic function (i.e. the transfer of a phosphate group from the HK to its RR partner) is simple to articulate, deciphering the molecular details of this process has proven anything but simple, especially when quantitative aspects come into play. Bouillet et al. report a series of elegant and sophisticated experiments to quantitatively understand HK functions, clearing up several open questions and providing a new strategy for future work in the field.