The initial search for attention-deficit hyperactivity disorder (ADHD) genes was hypothesis driven and focused on genes involved in neurotransmission, based on evidence from effective pharmacotherapeutic agents, animal model, and neuroimaging studies. Candidate genes, linkage, and genome-wide analyses studies (GWAS) have identified several gene variants involved in neurotransmission which confer a modest risk for ADHD. It is also possible that few common variants conferring risk for ADHD exist in the European population and that very large samples will be necessary to identify them. Structural variant studies are indicating that ADHD genetic risk is likely to be transmitted largely by rare variants that collectively disrupt a sizable constellation of genes, presumably with related functions. This is supported by animal genetic models which also implicate numerous genes involved in complex interactions between neural pathways. Epigenetic factors, environmental factors, and gene regulatory elements most likely also play a role in ADHD genetics.