This article reviews research on issues surrounding postsecondary transitions for youth in middle (North Central, Central, and South Central) Appalachia, a region that faces numerous education challenges because of its geography, poverty, and economy. Examining published research and data from 1995 to 2015, the review seeks to inform education policymakers, practitioners, and researchers about the current context, successes, challenges, and opportunities for students as they transition to adult life and to suggest directions for supporting postsecondary transitions. The review finds that high school graduation rates have improved, many youth are committed to the region, and numerous initiatives are underway to support successful postsecondary transitions. Challenges include limited job opportunities and possible misalignment with career preparation programs, high unemployment, and lack of postsecondary education experience and understanding among many adults. Implications include a need for more research on the nature and rigor of preparation in high schools and postsecondary institutions, development of place-based approaches, improved postsecondary transition awareness and support programs that involve parents, and more research on career choices of non-college-bound students.