Early-onset disorders (e.g., conduct problems, autism) show a marked male preponderance, whereas adolescent-onset disorders (e.g., depression, anxiety) show a marked female preponderance. A developmental psychopathology framework provides a means to investigate complex gender-related etiologies of these different disorders. This review focuses on biological and environmental factors implicated in the development of conduct problems and depression in boys and girls. Boys and girls showed certain differences in types, rates, comorbidities, antecedents, correlates, and trajectories of these problems. Origins of male and female preponderant problems are likely to be rooted, in part, in biological, physical, cognitive, and social-emotional differences in boys and girls that can precede the expression of clinical problems. These male-like and female-like characteristics are considered regarding conduct problems and depression to explore how they inform biological and environmental theories about gender and psychopathology. At the same time, because boys and girls also show many similarities, it is important to avoid sex-stereotyping mental health problems.