Menopause is a normal phenomenon in a woman’s life cycle involving multiple health-related issues that contribute to physical instability. Changes in the immune system in postmenopausal women are caused by estrogen deprivation along with age. Increased proinflammatory serum marker levels, cytokine responses in body cells, decreased CD4 T and B lymphocyte levels, and natural killer cell cytotoxic activity are also observed during postmenopause. Moreover, vitamin D, in addition to its classical effects on calcium homeostasis and bone density, plays an important role. Current evidence indicates that vitamin D regulates innate and adaptive immune responses; however, vitamin D deficiency is linked to increased autoimmune activity and infection susceptibility. This review provides an overview of the consequences of immune alterations as an outcome of aging in postmenopausal women and the benefit of vitamin D supplementation.