Holistic nursing is a discipline focused on healing the whole person and dedicated to understanding and supporting the premise of holistic health of the patient and promoting healing in practitioners, patients, families, social groups, and communities. An explication of knowledge related to caring and healing in the human health experience and in holistic nursing is informed by the individual nurse's paradigmatic stance. Holistic nursing research is complex and focuses on healing, particularly healing of self, others, systems, and communities at large. This article discusses the competing paradigmatic perspectives, theoretic perspectives supporting holistic research, fundamental patterns of knowing and knowledge generation, a framework for holistic research, and the challenges of conducting holistic research. Recommendations for future research agenda are presented.