This study is an excellent demonstration of the mechanistic insight that can be achieved using advanced single-molecule imaging in an in vivo setting. The extremely long single-molecule observation times (several minutes, versus the few seconds at most that can be achieved using typical photoactivatable GFP derivatives), achieved with the combination of Halo-tagging of protein replisome subunits, long exposures and sophisticated image analysis, allowed the measurement of the residence times of many replisome subunits on the yeast replisome. This important technical advance offered surprising results about the stability of the replisome machinery – notably, that the leading and lagging strand polymerases, Pol δ and Pol ε, are stably bound to the replisome. The study offers the opportunity for instructive comparisons with in vitro results as well as with organisms of different complexity (notably bacteria). The methodology is also fairly general and can be used or adapted to allow studies of macromolecular machineries in many live-cell settings on many organisms.