In vitro models utilizing cells in planar two-dimensional (2D) cultures do not reflect the in vivo environment and are increasingly replaced by three-dimensional (3D) cultures. Fundamental differences between 2D and 3D cell cultures systems include cell attach, spread and grow, their morphology, proliferation, differentiation or gene and protein expression. For that reason 3D models have been proven to be invaluable tools of study for the various fields of science, such as drug discovery, cancer research, differentiation studies or neuroscience. In the present review, we discuss 3D neural in vitro models that might provide important insides about the mechanisms of pathogenesis of neurodegenerative diseases.