For the yoga research community to capitalize on its current momentum, it is critical to consider certain developments in research theory and innovative methodologies. The concept of model validity must be incorporated in yoga therapy research so that explanatory constructs employed and outcome measures chosen reflect the principles of traditional yogic science. Focusing on effectiveness research will ensure maximum generalizability of study results and reflect real-world therapy delivery settings, thereby increasing the relevance of outcomes. Whole systems of healing require research methodologies that address complex relationships between multi-target therapies with multiple potential treatment results. Complex, dynamic systems theory provides the theoretical and methodological innovations necessary to design studies, choose outcomes, and analyze data in a way that can account for charting complex, cyclical, therapeutic trajectories across time. Emphasizing patient-centered outcomes is aligned with the patent-oriented and tailored natured of yoga therapy delivery. Increasing the quality and quantity of comparative effectiveness research to analyze the harms and benefits of contrasting therapies can provide an infrastructure for designing studies that can have significant practical impact. The creation of practice-based research networks within the yoga research community will incentivize links between mainstream clinical researchers and yoga therapy delivery settings, ultimately developing collaborative networks. Yoga therapy centers can facilitate patient recruitment for studies and inform standards for yoga researchers. Collaborative efforts between the yoga and ayurvedic research communities will streamline efforts, solidify expertise, cross-pollinate theoretical and methodological innovation, and consolidate efforts to secure research funding and increase publication and dissemination of study findings.