Effector proteins interact with GTPases in their active/GTP-bound state. To achieve this specificity, all effector proteins interact with Rab proteins via a similar Rab surface area which shows the largest conformational changes upon nucleotide exchange. This surface is also involved in the interaction with other Rab interacting proteins. In spite of the high structural similarity of the Rab proteins, the Rab binding domains of effector proteins display a large structural diversity. Structural comparison of uncomplexed activated Rab proteins and Rab:effector complexes reveals two distinct binding mode, that can be defined as key-lock or induced-fit mechanism (depending on conformational change upon binding). Generally, the specificity of Rab:effector interactions seems to be determined by surface residues on the Rab protein. In addition, the structural plasticity and conformational stability of the Rab proteins are crucial for their specificity.