This paper conceptualizes substance abuse as a disease of disconnection, which progressively separates and isolates people from relationships that can help them reduce their risk, promote their recovery, and ensure their health and well-being. Examining, in particular, substance abuse among women, the author explores how women often use drugs or alcohol in two ways: 1. to facilitate and establish connections with others, such as intimate partners, peers, and social groups, and/or 2. to cope with serious relational disruptions, violations, or trauma. In response, the author proposes a relational approach to prevention that emphasizes collaboration and the development of growth-fostering interpersonal, professional, and community relationships‹prevention through connection. Using an example from a college setting, this paper describes how everyone can participate in a relational approach to prevention, opening the way to new possibilities and opportunities to reduce high-risk substance use and abuse. This paper will appear as a chapter in an upcoming casebook on Relational-Cultural Theory, edited by Wendy Rosen and Maureen Walker to be published by Guilford Press.