Neuron-on-chip (NoC) systems-microfluidic devices in which neurons are cultured-have become a promising alternative to replace or minimize the use of animal models and have greatly facilitated in vitro research. Here, we review and discuss current developments in neuron-on-chip platforms, with a particular emphasis on existing biological models, culturing techniques, biomaterials, and topologies. We also discuss how the architecture, flow, and gradients affect neuronal growth, differentiation, and development. Finally, we discuss some of the most recent applications of NoCs in fundamental research (i.e., studies on the effects of electrical, mechanical/topological, or chemical stimuli) and in disease modeling.