Alcoholism and drug dependence are common psychiatric disorders with a heritability of about 50%; therefore genetic and environmental influences are equally important. Early-life stress is a predictor of adolescent problem drinking/drug use and alcohol/drug dependence in adulthood, but moderating factors governing the availability of alcohol/drug are important. The risk-resilience balance for addiction may be due in part to the interaction between genetic variation and environment stressors (G × E); this has been confirmed by twin studies of inferred genetic risk. Measured genotype studies to detect G × E effects have used a range of alcohol consumption and diagnostic phenotypes and stressors ranging from early-life to adulthood past year life events. In this article, the current state of the field is critically reviewed and suggestions are put forth for future research.