Rab GTPases and their regulatory proteins play a crucial role in vesiclemediated membrane trafficking. During vesicle membrane tethering Rab GTPases are activated by GEFs (guanine nucleotide exchange factors) and then inactivated by GAPs (GTPase activating proteins). Recent evidence shows that in addition to activating and inactivating Rab GTPases, both Rab GEFs and GAPs directly contribute to membrane tethering events during vesicle traffic. Other studies have extended the range of processes in which Rabs function, and revealed roles for Rabs and their GAPs in the regulation of autophagy. Here we will discuss these advances and the emerging relationship between the domain architectures of Rab GEFs and vesicle coat protein complexes linked with GTPases of the Sar, ARF and Arl families in animal cells. Rab GTPases underpin eukaryotic membrane traffic Soon after their discovery three decades ago, it was appreciated that Rab GTPases localise to specific membrane domains and organelle membranes within eukaryotic cells [1]. This led to the idea that Rab GTPases proofread the interaction between a vesicle and its target membrane prior to the membrane fusion reaction and thus act as key regulators of membrane traffic [2]. Subsequently, this idea has been further developed based on observations that Rabs recruit the components of physical tethers to membrane surfaces during vesicle docking [1]. To fulfil this function, Rabs interact with specific effector proteins and must be activated and inactivated in a manner that is coordinated with the processes of vesicle formation, by coat protein complexes, and vesicle fusion, mediated by the SNARE proteins (Figure 1A and 1B).