Kinesins are microtubule‐dependent motors that serve a multitude of cellular purposes. The conserved motor domain provides the energy required for these processes. Shortly after the solution of the first kinesin motor domain crystal structures the similarity to myosin and G‐proteins was noted. By analogy, it was suspected that regions flanking the γ‐phosphate group of the nucleotide (in particular the so‐called switch I and II regions) play important roles in the catalytic mechanism and the communication between the nucleotide cleft and the microtubule binding site. Since then, mutational analyses have supported this notion. Moreover, additional high‐resolution structures have demonstrated that the switch regions can assume variable conformations. In one case, a comparison of an ADP state and an ATP‐like state indicates a crucial involvement of the helix flanking switch II in modulating microtubule affinity. High‐resolution structures of a kinesin‐related protein mutated in the switch regions confirm the correlation between structural features in the switch vicinity and coupling of microtubule binding and nucleotide state.