Early-onset disruptive, aggressive, and antisocial behavior is persistent, can become increasingly serious as children grow older, and is difficult to change. In 2007, our group proposed a theoretical model highlighting the interplay between neurobiological deficits and cognitive and emotional functioning as mediators of the link between genetic influences and early social adversity, on the one hand, and antisocial behavioral problems in childhood, on the other. In this article, we review the post-2007 evidence relevant to this model. We discuss research on genetics/epigenetics, stress/arousal regulation, and emotion and executive functioning in support of the argument that antisocial children, especially those who persist in engaging in antisocial behavior as they grow older, have a range of neuropsychological characteristics that are important in explaining individual differences in the severity and persistence of antisocial behavior. Current clinical practice tends not to acknowledge these individual neuropsychological risk factors or to target them for intervention. We argue that aggressive and disruptive behavior in childhood should be regarded as a neurodevelopmental problem and that intervening at the level of mediating neuropsychological processes represents a promising way forward in tackling these serious behavioral problems.