•Discovered in yeast, Septins are molecularly and functionally conserved in vertebrates.•Septins form various heteropolymers regulating membrane and cytoskeleton dynamics.•Septins control neuron progenitor and neuron polarity.•Septins contribute to shape subcellular and molecular compartments. Septins, discovered almost half a century ago in yeast, have prominent contributions in a broad range of morphological and functional processes from yeast to human. Septins now emerge as key players of neurodevelopment and more specifically of the mechanisms driving the complex morphological differentiation and compartmentalization of neurons that are fundamental to their function. We review here recent advances in Septin-mediated processes of neuron differentiation, which enlighten similarities and differences between neuron and yeast polarity programs.