Docking interactions are key to understand the dynamic assembly of signal transduction complexes in the cell. In particular, the docking domain (D domain)-dependent interactions described so far for several MAPK routes are essential to specify the upstream regulators, downstream mediators and also inactivators that complex with the p38, JNK and ERK proteins. In addition to contributing to the maintenance of the linearity and specificity of these pathways, novel data have revealed that docking contacts also regulate the activity, subcellular distribution and substrate selection of each MAPK. Moreover, phosphorylation inside or around a docking domain is emerging as a novel mechanism of regulation of MAPK association with cellular partners, suggesting new potential strategies for the design of selective MAPK inhibitors. Here, we discuss these novel data and the biochemical and cellular implications they may have with specific emphasis on the p38 route.