Although the efficacy of nutritional intervention in autistic children has been evaluated in numerous reports in the literature, these studies are generally considered inconclusive. Despite positive results, most have been criticized for small sample size, poor study design, lack of placebo group, heterogeneity of diagnosis, and/or efficacy based on subjective parent report. Because of these limitations, none of the studies have successfully demonstrated that targeted nutritional supplementation can be an efficacious treatment approach for autistic children. Consequently, there is a real need for large well-designed placebo-controlled studies with intervention strategies based on metabolic or nutritional endpoints that can be followed for treatment efficacy and related to quantitative improvements in standardized behavioral testing conducted in a blinded manner.