Depression is a common and disabling psychiatric disorder in later life. Particular frail nursing home patients seem to be at increased risk. Nursing home-based studies on risk indicators of depression are scarce. Prevalence and risk indicators of depression were assessed in 333 nursing home patients living on somatic wards of 14 nursing homes in the North West of the Netherlands. Depressive symptoms were measured by means of the Geriatric Depression Scale (GDS). Major and minor depression were diagnosed according to the DSM-IV criteria, sub-clinical depression was defined as a GDS score >10 while not meeting the DSM-V criteria for depression. The prevalence of major depression was assessed to be 8.1% and the prevalence of minor depression was 14.1%, while a further 24% of the patients suffered from sub-clinical depression. For major depression significant risk indicators were found for pain, functional limitations, visual impairment, stroke, loneliness, lack of social support, negative life events and perceived inadequacy of care. For sub-clinical depression the same risk indicators were found, with the exception of lack of social support. Data were collected cross-sectional. The prevalence of depression in the nursing home population is very high. Whichever way defined, the prevalence rates found were three to four times higher than in the community-dwelling elderly. Age, pain, visual impairment, stroke, functional limitations, negative life events, loneliness, lack of social support and perceived inadequacy of care were found to be risk indicators for depression. Consequently, optimal physical treatment and special attention and focus on psychosocial factors must be major goals in developing care programs for this frail population.