The research literature notes both biological and operant theories of behavior disorder in individuals with intellectual disabilities. These two theories of genetic predisposition and operant reinforcement remain quite distinct; neither theory on its own is sufficient to explain challenging behavior in genetic syndromes and an integrated approach is required. This literature review integrates the two approaches by exploring how environmental factors can influence problem behavior in genetic syndromes associated with intellectual disability. Particular attention is paid to studies that describe evidence that problem behaviors in syndromes that are considered to be phenotypic are associated with other aspects of an established behavioral phenotype. The review highlights how the study of phenotype-environment interactions within syndromes can promote understanding of the aetiology of problem behaviors both within genetic syndromes and, ultimately, the wider population of individuals with severe intellectual disabilities. The review also evaluates the current status of research and the methods typically employed. Implications for intervention, future research and extending existing causal models of challenging behavior are discussed. (Contains 5 tables.)