The specificity of genetic and environmental risk factors for illicit substance use and substance use disorders (SUD) was investigated by utilizing self and co-twin reports in 1,791 male twins. There was a high rate of comorbidity between both use of, and SUD from, different classes of illicit substances. For substance use, the model that included one common genetic, one shared environmental, and one individual-specific (i.e., unique) environmental factor, along with substance-specific effects that were attributed entirely to genetic factors fit the data best. For illicit SUD, one common genetic and one common unique environmental risk factor, and substance specific shared environmental and unique environmental risk factors were identified. Risk factors for illicit substance use and SUD are mainly non-specific to substance class. Co-twin rating of illicit substance use and SUD was a reliable source of information, and by taking account of random and systematic measurement error, environmental exposures unique to the individual were of lesser importance than found in earlier studies.