Late life depression is highly prevalent disease which violently affects health and shortens life span. WHO expects depression to become the first leading cause of disease burden by the year 2030. There are evidences from depressed people including elderly that oxidative damage and immune-inflammatory activation play a role in depression and there is a need or extensive studies on links between this biological systems. The problem of how depression is related to immune system in elderly is complicated, as immune system shows many age-dependent changes and there is a growing body of data concerning the complex process of immunosenescence. Main alteration in immune functions in aging concern low-grade inflammatory activity and altered acute phase response, level of T cells and neutrophils functions. There is evidence that systemic inflammation is related to local pathology in the CNS and in consequence alter neuroplastic processes and lead to depression. There is also evidence that brain-endocrine-immune response in successful aging is correlated with metallothioneines (MTs) and therefore homeostasis of zinc. Aging significantly disturbs the functional role of MTs leading to zinc deficiency. Decreased level of zinc , even within the reference values, affects activity of antioxidant zinc-dependent enzymes, multiple aspects of innate and adaptive immunity and psychological dimensions in elderly.