Background: Hirudotherapy — the therapeutic application of medicinal leeches (Hirudo medicinalis and related species) — is one of the oldest biological treatments known to humanity, with documented use extending back to ancient Egypt, Greece, and India.[1,2] Within Ayurvedic medicine, the practice is systematically codified as Jalaukavacharana, a sub-procedure of Raktamokshana (bloodletting), described extensively in the Sushruta Samhita and Charaka Samhita.[33] Despite its ancient origins, modern pharmacological and molecular research has revealed that leech saliva contains more than 100 bioactive compounds that exert potent anticoagulant, anti-inflammatory, analgesic, and antimicrobial effects.[3,5]Objective: This review critically synthesizes PubMed-indexed literature on hirudotherapy, medicinal leech therapy (MLT), and Jalaukavacharana (JA) to provide a comprehensive, evidence-graded summary of mechanisms of action, species classification, clinical applications, Ayurvedic perspectives, safety profiles, complications, and future research directions.Methods: A comprehensive electronic search was conducted across PubMed/MEDLINE, Cochrane Library, Scopus, and DHARA databases using the MeSH terms and keywords: "hirudotherapy," "medicinal leech therapy," Hirudo medicinalis, "Jalaukavacharana," "Raktamokshana," and "leech saliva." Publications from 1990 to March 2026 in English were screened. A total of 118 articles meeting inclusion criteria were analyzed, including randomized controlled trials (RCTs), systematic reviews, observational studies, and case reports. Results: More than 20 pharmacologically identified bioactive compounds in leech saliva — including hirudin, calin, saratin, hyaluronidase, destabilase, and eglins — account for the diverse therapeutic actions of MLT.[5,6,26,27,28] Strong evidence supports hirudotherapy in venous congestion and flap salvage in reconstructive surgery.[12] Moderate-to-strong evidence exists for knee osteoarthritis and chronic low back pain.[9,10,11] Preliminary evidence supports use in varicose veins, thrombophlebitis, hemorrhoids, skin disorders, and selected ophthalmic conditions.[16,17,25] Ayurvedic applications described in Jalaukavacharana are largely consistent with modern biochemical understanding.[8,15,33] Key safety concerns include Aeromonas spp. infection, requiring antibiotic prophylaxis, and excessive bleeding.[13,24]Conclusion: Hirudotherapy occupies a unique and validated position at the intersection of traditional and modern medicine. It is an FDA-cleared modality for surgical applications[12] and merits continued rigorous investigation for a broader range of chronic inflammatory and musculoskeletal conditions. The integration of Jalaukavacharana into evidence-based Ayurvedic practice represents a promising domain for future clinical trials.[8,15] Keywords: Hirudotherapy; Medicinal leech therapy; Hirudo medicinalis; Jalaukavacharana; Raktamokshana; Leech saliva; Hirudin; Ayurveda; Complementary medicine; Osteoarthritis; Flap salvage.