Let be a graph of order , , and let be the set of vertices in that have a neighbor in . The differential of a set is defined as , and the differential of the graph is defined as . In this paper, we obtain several tight bounds for the differential in Cartesian product graphs. In particular, we relate the differential in Cartesian product graphs with some known parameters of , namely, its domination number, its maximum and minimum degree, and its order. Furthermore, we compute explicitly the differential of some classes of product graphs.