The prevalence of autism has been recently shown as a 20-30 fold increase globally since the early 1970s. Recent estimates from the Centers for Disease Control and Prevention (CDC) have determined about 1 in 68 children are affected with autism spectrum disorder (ASD). In 1995, the Greenwood Genetic Center began the South Carolina Autism Project as an ongoing research effort to identify the causes of autism. Traditional screening methods such as Sanger sequencing have not significantly impacted clinical yield due to the high degree of genetic heterogeneity associated with ASD. Fortunately, targeted Next Generation Sequencing (NGS) Panels now provide a cost-effective approach for studying individuals with overlapping phenotypic features and for disorders with genetic heterogeneity. However, the major limitation of NGS technologies is their inability to detect large deletions or duplications which either span an entire exon or involve multiple exons within a gene. High resolution microarrays are currently used to identify these types of alterations. In a collaborative effort with Agilent Technologies, we developed both a 92-gene Autism NGS Panel and a custom high-density, exon-centric microarray in an effort to provide more answers to families affected by ASD. Our results demonstrate the utility and complementary nature of both technologies in providing a more comprehensive genetic analysis of autism.