Until recently, genetic approaches in psychiatric disease had enjoyed limited success, but large-scale collaborative genome-wide association studies (GWAS) have now begun to identify common and rare variants associated with schizophrenia, bipolar disorder, and autism spectrum disorders [1–11]. An alternative to these agnostic, large-scale approaches is to focus instead on phenotypes thought to reflect disease processes. In this review, we refer to these phenotypes as intermediate phenotypes, rather than endophenotypes.