This paper investigates challenges that states, local school districts, and individual high schools face—and possible actions that need to be taken —in order to prepare all youth with the academic and career readiness skills needed to be successful in the global labor market. It identifies five broad policy and practice areas that must be addressed by policy makers at the national, state, and local levels to tackle what high schools can do to alter their approaches for meeting the multiple and complex challenges of all their students: (1) Instruction, Curriculum, and Structure; (2) Assessment Practices; (3) Graduation Requirements; (4) Community and Family Connections; and, (5) Data Quality Challenges.