Rab GTPases have been found in all eukaryotes, constituting the largest family of small GTPases. Rabs cycle between GDP- and GTP-bound forms and the active-site regions termed Switch I and II undergo the largest conformational changes between the two states. In the active form, they interact with effector proteins to regulate specific vesicle trafficking events such as docking, budding, motility or fusion. An intriguing question concerns the mechanism by which Rab GTPases generate specificity for a diverse spectrum of effectors and regulatory factors. This study focuses on the characterization of the structural differences between Rab11b and Rab11a GTPases. Rab11 plays an essential role in protein recycling from endosomes to the plasma membrane, polarized transport in epithelial cells, as well as traffic to the Golgi apparatus and phagocytosis. Rab11 has been identified as two isoforms (A and B) whose differential roles remain unclear. In this work, Rab11b was crystallized in its inactive and active forms. The structures were solved by molecular replacement at 1.55 and 1.95 Å resolution, respectively, and confronted with Rab11a structure (Pasqualato et al, 2004 JBC 279: 11480-11488). Rab11b and Rab11a crystal structures show striking differences. Inactive Rab11a has been crystallized as a dimer with a large interaction interface, leading to speculations about regulatory mechanisms through dimerization. Inactive Rab11b crystallized as a monomer and no dimers were detected in solution. Furthermore, active Rab11 isoforms display unique interactions in the nucleotide binding site that may explain possible functional differences. These differences may be important for the regulation of these proteins showing high overall 3D structure similarity.