More women than men receive a diagnosis of depression and more men than women receive a diagnosis of substance use disorder. The purpose of the present study was to examine the relevance of gender in assessing the risk factors of the two disorders over the life course from childhood to emerging adulthood. The theoretical perspective that framed the design of the study centered on a developmental cumulative stress/resource model. The model places emphasis on a life trajectory of risk factors that is marked by linkages between negative conditions and family circumstances, maladaptive peer relations, and schooling problems in childhood and stresses, socioeconomic disadvantage, and personal resource deficiencies in adulthood. The question of gender specificity was examined in two ways. (1) Variable-centered analysis modeled life trajectories leading to depression and substance use disorder, and (2) person-centered analysis defined the profiles of individuals who shared similar life patterns of risk and resources, and determined the causal attributions of those who were depressed. Data spanning 25 years were provided by 617 participants of the Concordia Longitudinal Risk Project. In line with epidemiological reports, more women than men met the diagnostic criteria for depression and more men than women qualified for a diagnosis of substance use disorder. The results of structural equation modeling indicated that the male and female patterns of relationships among the child and adult variables that defined the life trajectories to depression and substance use disorder were essentially alike. There were a number of gender differences, however. Characterizing the women more than the men were linkages in childhood between family adversity and social withdrawal and between quality of peer relations and school performance. In addition, childhood aggression in the women but not the men mediated the association between family adversity in childhood and disadvantaged socioeconomic position in adulthood. The results of latent class analysis provided another perspective on the relevance of gender. Five distinct configurations of risk factors were associated with depression and substance use disorder. The most and least advantaged of the profiles comprised a greater proportion of women than men, but both genders were equally represented in the profiles with less extreme patterns. Also, the clustering of aggression, elevated stress, and low socioeconomic position predicted depression and substance use disorder in both the men and women. Finally, there were gender differences in causal attributions. Men were more likely to attribute their depression to ongoing interpersonal conflict, and women to cite negative experiences in childhood as a causal factor. The findings of the study suggest that gender differences in the prevalence rates of depression and substance use disorder may best be explained by differences in help-seeking behaviour, in symptom reporting contexts and conditions, and in gender-related exposure to particular kinds of stress and modes of coping. More research along these lines is warranted