Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTD) are two ends of a disease spectrum. Comprehensive summary of studies that use iPSC-derived neurons to model ALS and FTD. Balanced discussions on the unique capabilities of iPSC-derived neurons that capture some key features of ALS and FTD. Highlight the potentials of iPSC-derived neurons in drug discovery and therapeutics. Identify critical caveats that require improvements before iPSC-derived neurons can become highly effective disease models.