Anxiety and stress-related disorders are common and debilitating mental diseases. Genetic factors as well as environmental factors and life events contribute to their pathogenesis and partly mediate treatment response. However, these disorders are clinically heterogeneous, genetically complex, and the exact genetic causes are still unclear. Recently, some evidence has emerged for structural variation including copy number variants and small deletions/duplications to be associated with mental disorders. Here, the current state of knowledge on the role of genomic structural variation in affective, anxiety and stress-related disorders is reviewed, followed by a critical discussion of present methods to detect structural changes, future directions, and clinical implications including a potential role in personalized medicine.