This project aimed to explore the perspectives of entertainment industry and health communication practitioners in the United States on creating health storylines in entertainment programming. These dual perspectives are usually not studied in tandem but together offer insights into the creation of impactful health-related narratives. In-depth interviews were conducted with entertainment industry and health professionals ( N = 6) who are experienced in creating health storylines. Questions aimed to illuminate how practitioners define ‘success’ of a health storyline, what they perceive as key elements for impactful health storylines, how key story elements are created and the nature of collaboration between the entertainment industry and public health. Grounded theory analysis identified three core themes for the successful combination of narrative entertainment and health: choosing teams with complementary strengths (e.g., leveraging professional collaboration and trust), knowing your audience (e.g., conducting formative research to understand who the story is intended for and why) and integrating health content in authentic ways (e.g., telling dramatic stories with universal themes, without creating from the intent of relaying health information). Best-practice guidelines for narrative entertainment to communicate about health, informed by the core themes and persuasion theory, are offered for narrative development, pre-production, content creation and dissemination.