Policy-makers who are making decisions on sexuality education programs face important economic questions: what are the costs of developing sexuality education programs; and what are the costs of implementing and scaling them up? This study responds to these questions by assessing the costs of six school-based sexuality education programs (Nigeria, Kenya, Indonesia, India, Estonia and the Netherlands). Cost analyses were carried out in schools that were fully implementing a SE program, as this best reflects the resources needed to run an effective program. The costs were analyzed from the program perspective, meaning that all costs borne by the governmental and (international) non-governmental organizations supporting the program were included. Cost analyses were based on financial records, interviews and school surveys. The authors distinguished costs in three consecutive program phases: development, update and implementation. Recommendations on the most efficient program characteristics and scale-up pathways were drawn from results of three fully scaled up programs (Estonia, Nigeria and the Netherlands), scale-up scenarios of two pilot programs (Kenya and Indonesia), and an implementation plan (India), The costs of the programs were compared by converting cost per student reached in US dollars (US$) to international dollars (I$). Findings revealed a range of costs and coverage of sexuality education programs. Costs per student reached were; US$7 in Nigeria, US$13.50 in India, US$33 in Estonia and the Netherlands, US$50 in Kenya, and US$160 in Indonesia. Intra-curricular sexuality education programs have, because of their compulsory nature, the most potential to be scaled up and are therefore most efficient. Extra-curricular sexuality education programs have lower potential to be scaled up and are therefore less efficient. In terms of class size and number of lessons, countries need to strike a balance between the quality (demanding smaller classes and many lessons) and the costs (demanding larger classes and fewer lessons). Advocacy was a significant cost component.