This study sought to investigate the contribution of illness perceptions and coping mechanisms to the explanation of well-being of patients with Huntington's disease (HD). We investigated the Leventhal et al. assumption of the Self-regulation Model that coping mediates the relationship between illness perceptions and patients' well-being. Illness perceptions, coping, and well-being in 77 HD patients were assessed with validated questionnaires; motor performance and cognitive performance were assessed with Huntington's disease-specific measures. The assumption that illness perceptions influence HD patients' well-being via coping was not supported. The results indicate that both coping and illness perceptions made a major contribution to the explanation of variance in HD patients' psychosocial well-being. Variance in their physical well-being was explained by illness perceptions mainly. The need to conduct further research on the interrelationships between illness perceptions, coping, and well-being in this patient category is discussed.