Many young people experience social isolation and loneliness, which can have adverse effects on physical and psychological well-being. We propose that intergenerational relationships created through formal youth mentoring programs have the potential to reduce the social isolation of young people. Mentoring programs also enable adult volunteers to form new interpersonal connections. In addition, mentoring offers the possibility of strengthening the fabric of communities through engagement and interaction among participants from different social, racial, and economic backgrounds. Mentoring program goals, often influenced by sponsor priorities, rarely focus specifically on reducing social isolation and promoting human connections as primary outcomes, but shifting to this emphasis could promote greater attention to relational practice that prioritizes the inherent value of the mentoring relationship itself. Given the long history and widespread popularity of formal youth mentoring, we suggest the field offers practice expertise, research knowledge, and organizational infrastructure as a foundation for addressing social isolation among young people. However, we also caution that youth mentoring, as a relationship-based intervention, poses potential risks if not implemented well. Issues concerning power, ethics, and social justice need to be made explicit to ensure the support of intergenerational relationships that reduce rather than reproduce social patterns of oppression, stigmatization, and inequality.