Genetic, epigenetic and dietary factors and their interactions play a major role in brain development and the balance between its health and disease status. The dramatic developments in genomic and neuroimaging techniques are enabling researchers to study these interactions with new breadth and depth. This chapter provides a denition of key terms used to examine the relationship between genetics, diet, metabolism and brain function. Both TCF7L2 and APOE will be discussed and current knowledge regarding genetics and brain architecture and function will be reviewed.