Mental illness is a culturally laden phenomenon, and different cultures have unique ways of constructing mental illness. In this study, conceptions of mental illness were explored among 30 participants of Akan descent in Ghana through individual and group interviews. Participants demonstrated a wide range of knowledge on mental illness indicating that poor self-care, deficits in social functioning, and disordered behaviors are the cardinal features of mental illness. The data revealed that Akan cultural beliefs influenced notions of etiology of mental illness and care of the mentally ill. While participants recognized the role of multiple factors such as genetics, substance abuse, daily hassles (for example, concerns about basic needs such as food, clothing, and shelter), and trauma in the cause of mental illness, the predominant belief was that mental illness is a retributive and/or a spiritual illness. This belief encourages pluralistic health-seeking behaviors: use of hospitals, prayer camps, herbalists, and traditional healers. The implications of these findings for public health education on mental illness, and clinical training and practice are discussed.