BACKGROUND: Persons with disabilities are involved in self-employment (vocational rehabilitation) in microenterprises despite key role players not making valuable contributions or using self-employment as a placement option. OBJECTIVES: This research aimed to explore profitable self-employment microenterprises for persons with disabilities in rural South Africa. METHOD: This qualitative research study was conducted in a rural community in KwaZulu-Natal province, South Africa. Purposive and snowball sampling were used to recruit 10 persons with disabilities running profitable microenterprises for an average of 5 years each. Data were collected using a piloted question guide in a face-to-face interview. Thematic analysis followed the hybrid inductive and deductive approaches. RESULTS: Persons with disabilities participated, and 9 out of 10 were males. Two themes emerged. Theme one: Running microenterprises - self-initiated and maintained. They use their hands and minds to start microenterprises that benefit them and their families. Theme two: Multiple key role players should be involved in self-employment. Persons with disabilities perceive various key role players and themselves as having an active role in self-employment to benefit their microenterprises. CONCLUSION: Persons with disabilities in a rural setting engage in successful self-employment in microenterprises, which they self-initiate and maintain. Roles and responsibilities of persons with disabilities and key role players in and outside the hospital setting are crucial for those in self-employment. CONTRIBUTION: This research generated contextual data towards the under-researched subject on self-employment for persons with disabilities.