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Introduction: Dhatus, the fundamental tissues in Ayurveda, are critical for maintaining structural integrity, physiological functions, and overall health. Classical Samhitas describe seven primary Dhatus—Rasa, Rakta, Mamsa, Meda, Asthi, Majja, and Shukra—each with specific characteristics, functions, and interrelationships. Understanding Dhatu physiology is essential for disease prevention, diagnosis, and therapeutic interventions. Methods: A comprehensive literature review was conducted using classical Ayurvedic texts (Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya) and modern scientific databases (PubMed, Scopus, Web of Science). Keywords included “Dhatu,” “Ayurveda,” “Samhita,” “tissue physiology,” and “clinical relevance.” Inclusion criteria encompassed classical references and peer-reviewed studies exploring Dhatu physiology, pathology, and therapeutic approaches. Exclusion criteria were anecdotal or non-peer-reviewed sources. Results: Classical texts provide detailed descriptions of Dhatu formation, functions, interrelationships, and clinical significance. Modern interpretations align Dhatus with histological and biochemical correlates, linking them to blood components, muscle tissue, fat, bone marrow, skeletal system, nervous system, and reproductive tissues. Imbalances in Dhatus manifest as specific clinical disorders, guiding treatment strategies including Panchakarma, Rasayana, and lifestyle interventions. Discussion: Integrating classical Dhatu concepts with contemporary biomedical understanding offers insights into tissue-specific pathology, regenerative medicine, and personalized therapy. However, standardized diagnostic tools, quantifiable assessment methods, and translational research are required for clinical integration. Conclusion: Dhatu-based analysis remains a cornerstone in Ayurvedic clinical practice, offering a comprehensive framework for understanding tissue physiology and pathology. Bridging classical knowledge with modern scientific methods can enhance personalized healthcare, preventive strategies, and targeted therapeutics.

KEYWORDS: Ayurveda, Clinical relevance, Dhatu, Samhita, Tissue physiology