Background: Prevalence of depression is twice as high in women as in men, also in older adults. Lack of social support is a risk factor for late-life depression. The relation between depression and social support may be different for men and women. Methods: Data from the Longitudinal Aging Study Amsterdam were used to investigate gender differences in the relation between social support and depression in a population-based sample aged 5585 years, with n = 2,823 at baseline and using the 13-year follow-up data on onset of depression. Results: Respondents without a partner in the household, with a small network, and with low emotional support were more often depressed, with men showing higher rates of depression than women. A high need for affiliation was associated with depression in women but not in men. Lack of a partner in the household and having a small network predicted onset of depression in men but not in women. In respondents with high affiliation need and low social support, depression rates were higher, with men being more often depressed than women. Conclusions: Low social support and a high need for affiliation were related to depression in later life, with men being more vulnerable for depression than women. Considering the serious consequences of depression, especially in older people, it is important to identify the persons with low social support and a high need for affiliation, and to help them to increase their social support or to adjust their needs.