Today, more than half of the world population is under the age of 25 years and one in four is under age 18. The urgency of expanding access to Comprehensive Sexuality Education (CSE) notably for children and young people in Africa and Asia is greater than ever before. However, many challenges to the implementation and delivery of CSE in resource poor settings have been identified in the literature. CSE's effectiveness could be strongly improved if these challenges were better met. This paper aims to contribute to those much-needed improvements by sharing lessons learned from a decade of implementation of one particular CSE programme, "The World Starts With Me," among various populations in 11 low income countries in Africa and Asia. The aims, content, reach and effectiveness of the programme are described. Next, the challenges for implementation and delivery at student, teacher, school and context level are discussed with reference to the wider knowledge base in this area. Finally, suggestions are provided for ways forward including the increased sensitivity of programmes for normative and practical barriers to sexual health, further advancement towards gender transformativity, a far-reaching expansion of comprehensive forms of teacher training and coaching, and a serious stepping-up of multilevel "whole school" approaches.