Endocytosis and recycling are essential components of the wiring enabling cells to perceive extracellular signals and transduce them in a temporally and spatially controlled fashion, directly influencing not only the duration and intensity of the signaling output, but also their correct location. Here, we will discuss key experimental evidence that support how different internalization routes, the generation of diverse endomembrane platforms, and cycles of internalization and recycling ensure polarized compartmentalization of signals, regulating a number of physiological and pathologically-relevant processes in which the resolution of spatial information is vital for their execution.