Findings from Project Family are presented to illustrate how a partnership-based program of research on universal family- and youth-focused interventions is addressing a public health challenge. One aspect of this public health challenge is the high prevalence of youth problem behaviors and a second aspect concerns barriers to scaling-up empirically-supported preventive interventions designed to ameliorate those problem behaviors. Illustrative findings are presented within a conceptual framework for scaling-up preventive interventions to achieve greater public health impact. Three interrelated sets of research requirements and findings are addressed within this framework: (a) rigorously demonstrating intervention effectiveness; (b) attaining sufficient levels of intervention utilization in diverse general populations, requiring study of recruitment/retention strategies, cultural sensitivity, and economic viability; and (c) achieving implementation quality, involving investigation of adherence and dosage effects, along with theory-driven, intervention quality improvement. The paper concludes with discussion of the need for careful investigation of community-university partnership models as a key mechanism for large-scale implementation.