The compendium of articles in this monograph encompasses two interrelated themes currently emphasized in CEDAR's research. One line of research is directed at delineating the mechanisms underlying the development of a diagnosed substance use disorder (SUD). Genetic, biochemical, physiological, and psychological processes are investigated in conjunction with physical and social environment factors with the objective of elucidating the developmental pathway to SUD. Using a prospective paradigm the factors associated with the transition from no drug use to drug use to a diagnosis of abuse or dependence will be determined. Upon completion of this research, the individual's risk for transitioning from one phase to the next can be quantitatively specified. As documented in the various articles, the research findings accrued to date at CEDAR indicate that psychological dysregulation is an integral characteristic of SUD liability during childhood. The heuristic utility of this phenotype is underscored by emerging results demonstrating genetic (see Vanyukov et al.), biochemical (see Pajer et al.), maturational (see Kirillova et al.) and executive cognitive functioning influences (see Shoal and Giancola) on the expression of psychological dysregulation, which, in turn, predisposes to regular tobacco consumption during adolescence (see Reynolds et al.) and SUD by young adulthood (Tarter et al., submitted a). One important component of this research program pertains to delineating the factors that are specific to SUD liability in relation to comorbid outcomes such as suicide (see Cornelius et al.) and violence (Tarter et al., submitted b). A second line of research pertains to instrumentation development for practical and efficient assessment of the variables salient to SUD liability. Based on CEDAR's comprehensive protocols, several instruments have been provi- sionally developed. As discussed herein, these include a multidimensional measure of neglectful parenting (see Dunn et al.), a multidimensional schema for assessing substance use topology (see Kirisci and Tarter), a multi-informant questionnaire for assessing psychological dysregulation (see Mezzich et al.) and a multi-domain screening inventory of problems which commonly precede or emerge concomitant to substance use behavior (see Tarter and Kirisci). These instruments enhance clarification of SUD liability and potentially improve prediction accuracy of SUD outcome. Furthermore, investigations at CEDAR spearhead the application of diachronic evaluation; that is, assessment which is linked to discrete phases in the emergence of SUD (see Clark et al.). In the course of CEDAR's longitudinal research, technology transfer will thus be accomplished through development of new instrumentation designed to identify youth who are at high risk for SUD. In this fashion, prevention practice will be grounded in empirical research based on etiology of SUD. (Editor's abstract.)