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In this commentary I review the recent paper by Iyegbe et al. on "The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for gXe research". I discuss how the paper advances our knowledge of polygenic risk scores for use, amongst others, in gene-environment interaction studies and the opportunities and challenges such approaches will bring to our understanding of the epidemiology of psychotic disorders, including schizophrenia.