Innovative approaches are needed to make health communication research and practice more timely, responsive, and effective in a rapidly changing information ecosystem. In this paper we provide an overview of strategies that can enhance the delivery and effectiveness of health communication campaigns and interventions, as well as research approaches that can generate useful data and insights for decisionmakers and campaign designers, thereby reducing the research-to-practice gap. The discussion focuses on the following approaches: digital segmentation and microtargeting, social media influencer campaigns, recommender systems, adaptive interventions, A/B testing, efficient message testing protocols, rapid cycle iterative message testing, megastudies, and agent-based modeling. For each method highlighted, we also outline important practical and ethical considerations for utilizing the approach in the context of health communication research and practice, including issues related to transparency, privacy, equity, and potential for harm.