Personal Social Health and Economic (PSHE) education is a non-statutory school subject designed to facilitate the delivery of a number of key competencies relevant to health, safety and wellbeing. As well as contributing to learning objectives in regards to these topics PSHE education has been ascribed with weighty expectations for outcomes well beyond the classroom relating to physical, mental, sexual and emotional health and safety. This paper reviews a programme of research aimed at providing guidance for the evidence-based provision of PSHE education, including a summary of the major impediments and facilitators of evidence-based programming, as well as a model curriculum for the delivery of evidence-based PSHE. An extensive literature review was conducted along with a series of interviews with programme developers, researchers, teachers and other school practitioners with the aim of developing a cohesive rationale for PSHE education and identifying evidence-based programmes which could be implemented to contribute to PSHE aims. The proposed model curriculum is comprised of evidence-based programmes which are PSHE-relevant and applicable or adaptable to the PSHE-education implementation context. While the provision of evidence-based PSHE presents a number of challenges and is limited by a lack of resources and evidence of effectiveness, with appropriate guidance PSHE education can be improved so that a comprehensive syllabus of evidence-based programmes is enacted in secondary schools. This will increase the likelihood that PSHE has the intended effect on adolescent mental and physical health and wellbeing.