The current study expands on and integrates previous theoretical models concerning the pathways that link child maltreatment to substance use disorder. The proposed model, based on the self-medication hypothesis, suggests that experiences of neglect and abuse during childhood can lead to substance use and abuse both directly and indirectly, via dissociation resulting from failed attempts to integrate experiences of maltreatment in childhood. The model was tested on ten substances (painkillers, stimulants, sedatives, marijuana, cocaine, ecstasy, hallucinogens, heroin, inhalants, and methamphetamine) via structural equation modeling (SEM) in a sample comprising 1040 community-dwelling adults (67 % women) aged between 18 and 78 (M = 29.55, SD = 11.37). Fit indexes of the SEM were good, thus supporting the hypothesized model. Specific forms of child maltreatment were related to increased use of specific substances; however, experience of childhood neglect (both physical and emotional) was found to have a central role in predicting use of most substances. Although no single pathway can fully explain the origins of substance abuse, the current study provides evidence of a critical developmental pathway to it, with implications for theory and clinical practice.