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The region inhabited by the Luo ethnic group in Kenya is disease endemic. However, disease awareness initiatives register low acceptance due to the sociocultural images of disease and illness conceptualized in the local Dholuo language in ways that may contradict modern biomedical knowledge and practice. This article evaluates the sociocultural basis of encoding descriptions of disease in the Luo indigenous knowledge system and their implications for modern medical practice. The methodology entailed use of qualitative interviews of purposively sampled Dholuo-speaking patient escorts in a provincial referral hospital. Nonparticipant observation was also conducted at funerals to monitor contextualized usage of the discourse of disease, illness, and death. The data were analyzed using qualitative content analysis and categorized into emergent themes and categories. The results revealed that Dholuo is replete with expressions that emphasize the vulnerability and discrimination of the sick. Such attitudes cause rejection of interventions and negatively influence health-seeking behavior. The expressions were relevant and acceptable to cultural insiders; hence, they could determine their understanding of health conditions thereby influencing how they make medical decisions. It emerges that the unique Luo worldview controls their perceptions on the causes of disease and prescribes community-driven remedies which may depart from the expectations of the biomedical model.