Evidence for the positive outcomes of comprehensive sexuality education (CSE) on adolescent sexual and reproductive health (ASRH) is well documented. However, in many low- and middle-income countries (LMICs) this has not been translated into practice; although some form of sexuality education may be provided, a number of barriers exist that impede delivery of CSE that is in keeping with evidence-based, international guidance.Data gathered in 2015 in secondary schools in Ghana, Kenya, Peru and Guatemala, provide an in-depth understanding of a range of implementation bottlenecks at various levels, from national programme planning challenges to classroom level barriers. Based on this learning, this paper presents seven recommendations, which are applicable beyond these four countries, for overcoming common bottlenecks in LMICs and thereby improving CSE implementation.