Objectives of this study were to assess explanatory models (considering illness experience and meaning), addiction severity among patients with drug dependence, and the role of migration. Adapted Explanatory Model Interview Catalogue interviews were conducted with 70 outpatients in a Paris suburb. Among them, 42 were either first- or second-generation immigrants, most from North Africa. Explanatory models were analyzed qualitatively and quantitatively according to migration status, assessing potential confounders with multivariate linear models. Explanatory models were heterogeneous. Compared with nonmigrants, migrants reported fewer somatic and violence-related symptoms. They attributed the causes of their addiction more frequently to social and magico-religious factors and less to psychological factors. Conversely, no difference in addiction severity was found between migrants and nonmigrants. Considering local patterns of illness experience and meaning of drug dependence is a critical component of culturally sensitive clinical care.