Set in Espiritu Santo, Vanuatu, this study explores the relationship between cultural knowledge and beliefs concerning illness and health-seeking behaviour within the context of medical pluralism. Concentrating on the nation’s high rates of diabetes and non-communicable disease (NCD) risk factors, this research analyses the way in which understandings of disease aetiology and healing efficacy impact upon treatment-related decisions. Data were obtained through a mixed-methods community survey of 313 adult respondents developed in collaboration with ni-Vanuatu health experts, community leaders and survey enumerators, and comprised of open and closed-ended questions. As the results demonstrate, framed by cultural and religious beliefs, multifaceted indigenous conceptualizations of health and illness in Vanuatu are directly linked to pluralist health seeking practices, including the concurrent use of formal and informal health services. The interwoven identification of sociocultural, physical and clinical determinants of disease highlights the complex manner in which health is understood and maintained by ni-Vanuatu. In successfully addressing the rising burden of NCDs, it is integral that health interventions and service providers acknowledge the complex conceptualization of disease and ensure the provision of holistic care that embraces rather than ignores the steadfast role of local systems of belief, and of traditional, religious and other informal forms of healthcare provision.