Vesicle fusion is a ubiquitous biological process involved in membrane trafficking and a variety of specialised events such as exocytosis and neurite outgrowth. The energy to drive biological membrane fusion is provided by fusion proteins called SNAREs. Indeed, SNARE proteins play critical roles in neuronal development, neurotransmitter and hormone release. SNARE proteins form a very tight alpha-helical bundle which can pull two membranes together thereby initiating fusion. Whereas a great deal of attention has been paid to partner proteins which can affect SNARE function, recent genetic and biochemical evidence suggests that local lipid environment may be as important in SNARE regulation. I will discuss in detail regulation of the pivotal SNARE protein – syntaxin. Syntaxin together with its chaperone Munc18 constitute a molecular tandem essential for exocytosis in all eukaryotes. We previously showed that Munc18 inhibition of neuronal syntaxin1 can be overcome by arachidonic acid, suggesting that this common second messenger acts to disrupt the syntaxin/Munc18 interaction. Our recent data indicate that arachidonic acid can stimulate syntaxin1 alone indicating that it is syntaxin1 that undergoes a structural change in the syntaxin1/Munc18 complex. The same principle operates in the case of the ubiquitous syntaxin3 isoform highlighting the conserved nature of the mechanism of arachidonic acid action. We also show that syntaxin3 plays an important role in the growth of neurites and serves as a direct target for the dietary omega-3 fatty acids. Our findings provide a molecular basis for the previously established action of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) in cell membrane expansion and identify the first single effector molecule for these essential nutrients.