Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder with several known environmental and genetic causes. Narrowing down the long list of potential causes to find reasonable targets for biological intervention will be necessary for the development of new, effective medications. Adding to the complexity of understanding and treating this disorder is the disparity in diagnosis between the sexes. Here we review and organize findings from the ASD literature with a perspective of aberrant hormonal signaling contributing to changes in nuclear receptor-dependent gene expression, the downstream effects of which lead to ASD and explain the male tendency towards this diagnosis. Potential biomarkers for diagnosis and intervention are highlighted within the nuclear receptor perspective.