Autism represents a large spectrum of diverse individuals with varying underlying genetic architectures and needs. For some individuals, a single de novo or ultrarare genetic variant has a large effect on the intensity of specific dimensions of the phenotype, while, for others, a combination of thousands of variants commonly found in the general population are involved. The variants with large impact are found in up to 30% of autistic individuals presenting with intellectual disability, significant speech delay, motor delay, and/or seizures. The common variants are shared with those found in individuals with attention-deficit/hyperactivity disorder, major depressive disorders, greater educational attainment, and higher cognitive performance, suggesting overlapping genetic architectures. The genetic variants modulate the function of chromatin remodeling and synaptic proteins that influence the connectivity of neuronal circuits and, in interaction with the environment of each individual, the subsequent cognitive and personal trajectory of the child. Overall, this genetic heterogeneity mirrors the phenotypic diversity of autistic individuals and provides a helpful bridge between biomedical and neurodiversity perspectives. We propose that participative and multidisciplinary research should use this information to understand better the assessment, treatments, and accommodations that individuals with autism and families need.