Cell navigation is the process whereby cells or cytoplasmic extensions are guided from one point to another in multicellular organisms or, in the case of unicellular eukaryotic organisms, in the environment. Recent work has demonstrated that membrane trafficking plays an important role in this process. Here, we review the role of soluble N-ethylmaleimide-sensitive fusion attachment protein (SNAP) receptors (SNAREs), which constitute the core machinery for membrane fusion and are essential for intracellular vesicular trafficking. We discuss the important functions of several vesicular- and target-SNAREs, in particular vesicular-associated membrane proteins 1, 2, 3, 4 and 7; vti1a/b; SNAP23 and SNAP25; and syntaxins 1, 3, 6 and 13. We conclude that endosomal SNAREs are important for cell navigation, a concept that opens avenues for fundamental research. There are also possible therapeutic applications because some of these SNAREs are the targets of clostridial neurotoxins.