Examining the interplay of genes, experience and the brain is crucial to understanding psychopathology. We review the recent gene-environment interaction (G×E) and imaging genetics literature with the goal of developing models to bridge these approaches within single imaging gene-environment interaction (IG×E) studies. We explore challenges inherent in both G×E and imaging genetics and highlight studies that address these limitations. In specifying IG×E models, we examine statistical methods for combining these approaches, and explore plausible biological mechanisms (e.g. epigenetics) through which these conditional mechanisms can be understood. Finally, we discuss the potential contribution that IG×E studies can make to understanding psychopathology and developing more personalized and effective prevention and treatment.