In 2001, the World Health Organization (WHO) published its health report titled Mental Health: New Understanding, New Hope. According to this report, “Major depression is now the leading cause of disability globally and ranks fourth in the ten leading causes of the global burden of disease. If projections are correct, within the next 20 years, depression will have the dubious distinction of becoming the second cause of the global disease burden.” The report is dedicated to addressing the global burden of mental illness and examines the acute vulnerability to mental illness of those living in developing countries. Tanzania is among Africa’s poorest developing nations. Census data collected in 1999 indicates that most Tanzanians are living in conditions identified by WHO as risk factors for mental illness, including depression. The objective of this paper is to determine if mentally ill Tanzanians and those at risk for developing mental illness can benefit from culturally relevant variations of traditionally Western models for diagnosis and treatment. A review of the literature elucidates both Western and non-Western perspectives on mental health illness and care across cultures. Pertinent literature from various disciplines including psychology, psychiatry, and anthropology is reviewed. Findings indicate that culturally appropriate models for diagnosis and treatment of mental illness should be designed and used in developing nations, like Tanzania. Such models may be effective in preventing and alleviating psychological suffering globally.