Vitamin D, which is also known as “sunshine vitamin”, plays a pivotal role in both bones as well as non-bone organs. The ubiquitous expression of VDR in numerous tissues, including the kidney, heart, muscle, breast, colon, prostate, brain and immune cells, makes this as a natural target of modulation in disease pathogenesis including variety of cancers, metabolic syndrome, renal transplant and dermal disorders. Low vitamin D levels have become an epidemic across the continent irrespective of amount of sunshine during different seasons. The epidemiological studies estimate that currently at least 1 billion people suffer from low vitamin D levels. Vitamin D receptors regulate a number of signaling pathways. These pathways are often involved in inflammation and tumor growth and especially in the epithelial cells of the skin, breast, prostate and colon in case of cancer. Vitamin D plays important roles in calcium homeostasis, cell proliferation and cell differentiation to many target tissues, which is considered to be mediated through the nuclear VDR control of target genes. Vitamin D dysfunction may be in part inherited as suggested by previous research and VDR polymorphisms is perceived to be the primary reasons of this inherited dysfunction of VDR. This review discuses studies highlighting the role of vitamin D with more emphasis in metabolic syndrome, diabetes, breast, ovarian and prostate cancer, psoriasis, and allograft outcomes other than vitamin D’s traditional role related to bone health.