Background: Many children and adolescents with Down syndrome fail to achieve proficiency in mathematics. Researchers have suggested that tailoring interventions based on the behavioural phenotype may enhance efficacy. Method: The research questions that guided this review were (1) what types of mathematics interventions have been empirically evaluated with children and adolescents with Down syndrome?; (2) do the studies demonstrate sufficient methodological rigor?; (3) is there evidence of efficacy for the evaluated mathematics interventions?; and (4) to what extent have researchers considered aspects of the behavioural phenotype in selecting, designing and/or implementing mathematics interventions for children and adolescents with Down syndrome? Nine studies published between 1989 and 2012 were identified for inclusion. Results: Interventions predominantly focused on early mathematics skills and reported positive outcomes. However, no study met criteria for methodological rigor. Further, no authors explicitly considered the behavioural phenotype. Conclusions: Additional research using rigorous experimental designs is needed to evaluate the efficacy of mathematics interventions for children and adolescents with Down syndrome. Suggestions for considering the behavioural phenotype in future research are provided.