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The purpose of this qualitative study was to identify significant external and internal challenges that state organization leaders face in promoting science-based teen pregnancy prevention programs within their states. The state organization administrators were chosen because their organizations were funded by the U.S. Centers for Disease Control and Prevention (CDC) to promote science-based prevention programs between 2005 and 2010. Given a recent federal infusion of $155 million to replicate science-based programs nationwide, this study is timely. Data reported in this article were collected annually over three years (2006)(2007)(2008)(2009) using semi-structured interviews. External factors influencing success include the states' socio-political climate, including the impact of abstinence-only programs; internal factors include infrastructure, recruitment, and retention of key partners, organization, board, and staff management and financial sustainability.