The neonatal 6-OHDA-lesioned rat, coloboma mouse, DAT-KO mouse, and spontaneously hypertensive rat (SHR) models all bear a phenotypic resemblance to ADHD in that they express hyperactivity, inattention, and/or impulsivity. The models also illustrate the heterogeneity of ADHD: the initial cause (chemical depletion or genetic abnormality) of the ADHD-like behaviors is different for each model. Neurochemical and behavioral studies of the models indicate aberrations in monoaminergic neurotransmission. Hyperdopaminergic neurotransmission is implicated in the abnormal behavior of all models. Norepinephrine has a dual enhancing/inhibitory role in ADHD symptoms, and serotonin acts to inhibit abnormal dopamine and norepinephrine signaling. It is unlikely that symptoms arise from a single neurotransmitter dysfunction. Rather, studies of animal models of ADHD suggest that symptoms develop through the complex interactions of monoaminergic neurotransmitter systems.