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Introduction: Agni, the principle of digestion and metabolism, occupies a central place in Ayurveda. Classical Samhitas emphasize that derangements in Agni are the root cause of multiple diseases, making its understanding essential for clinical practice. Despite its ancient conceptual basis, modern research increasingly recognizes Agni’s relevance in gastrointestinal, metabolic, and systemic disorders. Methods: This review systematically analyzed references to Agni in Ayurvedic Samhitas including Charaka Samhita, Sushruta Samhita, Ashtanga Hridaya, and Kashyapa Samhita. A structured literature search was performed using PubMed, Scopus, and AYUSH Research Portal, focusing on articles published between 2000–2025. Keywords used included “Agni,” “Ayurveda metabolism,” “digestive fire,” and “clinical relevance of Agni.” Inclusion criteria comprised original research, reviews, and clinical studies directly discussing Agni or its correlates. Exclusion criteria included studies with limited methodological details and non-peer-reviewed sources. Results: Four primary types of Agni (Jatharagni, Bhutagni, Dhatvagni, and Pachakagni) were identified across Samhitas, with Jatharagni being the most emphasized. Clinical relevance of Agni extends to disorders such as Ajeerna, Grahani, Prameha, Sthoulya, and systemic inflammatory conditions. Modern literature correlates Agni with enzymatic digestion, gut microbiota, mitochondrial metabolism, and metabolic pathways. The review highlights convergences between Ayurveda’s Agni concept and modern insights into metabolism, immunology, and psychosomatic health. Discussion: While Ayurveda conceptualizes Agni holistically, modern science provides mechanistic correlates. However, empirical evidence directly validating Ayurvedic Agni remains limited. Future studies should focus on developing objective biomarkers, integrating clinical trials, and validating therapeutic interventions based on Agni assessment.

KEYWORDS: Agni, Ayurveda, Clinical relevance, Digestion, Samhitas