This paper explores adult (18-60years) patients’ perceptions of depression etiology in a Nigerian Tertiary Hospital. This was with a view to gaining a socio-cultural understanding of patients’ knowledge on depression etiology and its treatment. A structured questionnaire was administered on 78 clinically diagnosed depressed patients that have sought treatments at the hospital over a period of 5years (2002-2007). In-depth interviews were held with 14 Health Caregivers, while depressed patients’ case files were consulted for secondary data. Results indicated that 63.3 per cent of males and 77.6 per cent of females were between the ages of 18 - 40 years. There were more married females (60.71%) than males (39.29%). Patients perceived depression as a multidimensional health problem as they linked it to genetics, family background, stress or negative life experiences, loss of faith in God, and unhealthy lifestyle. Among the Health Caregivers a slight variation was observed compared to that of the patients. However, stress or negative life events as causal factors was significant for males (χ2= 7.6, p =.021) and females (χ2=19.4, p =.000) patients. On cure for depression, 70 per cent of males and 77.1 per cent of female patients disagreed that there was a cure. Patients’ conception of depression as a multi-causal phenomenon indicates diversity in beliefs which could influence their compliance to available treatment modes. Hence, harmonizing these divergences in the care process would be relevant for effective management of depression.