Despite significant advances in understanding the biological bases of autism spectrum disorder (ASD), the field remains primarily reliant on observational and parent report measures of behavior to guide clinical practice, conduct research, and evaluate intervention outcomes. There is a critical need for objective measures to more sensitively and validly quantify risk for ASD, ASD symptomatology, and its change in clinical trials. To maximize public health impact, such biomarkers must be cost effective and utilize accessible and scalable technologies. This letter describes concerns specific to the development of clinically practicable biomarkers for ASD and approaches to optimize understanding of these biomarkers through development of large-scale consortia and clinical networks.