The brain is a well-organized, yet highly complex, organ in the mammalian system. Most investigators use the whole brain, instead of a selected brain region(s), for biochemical analytes as toxicological endpoints. As a result, the obtained data is often of limited value, since their significance is compromised due to a reduced effect, and the investigators often arrive at an erroneous conclusion(s). By now, a plethora of knowledge reveals the brain regional variability for various biochemical/neurochemical determinants. This review describes the importance of brain regional heterogeneity in relation to cholinergic and noncholinergic determinants with particular reference to organophosphate (OP) and carbamate pesticides and OP nerve agents.