King Cobra (Ophiophagus hannah) has a significant place in many cultures, and is a medically important venomous snake in the world. Envenomation by this snake is highly lethal, manifested mainly by neurotoxicity and local tissue damage. King Cobra may be part of a larger species complex, and is widely distributed across Southeast Asia, southern China, northern and eastern regions as well as the Western Ghats of India, indicating potential geographical variation in
venom composition. There is, however, only one species-specific King Cobra
antivenom available worldwide that is produced in Thailand, using
venom from the snake of Thai origin. Issues relating to the management of King Cobra envenomation (e.g., variation in the composition and toxicity of the
venom, limited availability and efficacy of
antivenom), and challenges faced in the research of
venom (in particular proteomics), are rarely addressed. This article reviews the natural history and sociocultural importance of King Cobra, cases of
snakebite envenomation caused by this species, current practice of management (preclinical and clinical), and major toxinological studies of the
venom with a focus on
venom proteomics, toxicity and neutralization. Unfortunately, epidemiological data of King Cobra
bite is scarce, and
venom proteomes reported in various studies revealed marked discrepancies in details. Challenges, such as inconsistency in
snake venom sampling, varying methodology of proteomic analysis, lack of mechanistic and antivenomic studies, and controversy surrounding
antivenom use in treating King Cobra envenomation are herein discussed. Future directions are proposed, including the effort to establish a standard, comprehensive Pan-Asian proteomic database of
King Cobra venom, from which the
venom variation can be determined. Research should be undertaken to characterize the toxin antigenicity, and to develop an
antivenom with improved efficacy and wider geographical utility. The endeavors are aligned with the WHO´s roadmap that aims to reduce the disease burden of
snakebite by 50% before 2030.