Mathematics is an area of difficulty for most children and adolescents with Down syndrome (DS). Researchers have suggested tailoring academic interventions based on the behavioral phenotype of DS could improve mathematics outcomes. The purpose of this review was to examine whether children and adolescents with DS perform differentially compared to individuals without DS on mathematics tasks. Findings favoring differential performance may support the notion that the behavioral phenotype is important to consider in future mathematics intervention research. We identified eight studies published between 1989 and 2013 that compared mathematics performance of children and adolescents with DS to another group of individuals. No consistent pattern of differential performance for children with DS was found in the studies. More research is necessary to understand the connection between the behavioral phenotype of DS and mathematics performance.