1,25-dihydroxyvitamin D3 [1,25(OH)2D3] exerts its effects via the vitamin D receptor (VDR) that belongs to the steroid/thyroid hormone receptor superfamily leading to gene regulation mediating various biological responses. Within the last two decades, the receptor has been shown to be present not only in classical target tissues such as bone, kidney and intestine but also in many other non-classical tissues, e.g., in the immune system, in the reproductive system, in the endocrine system, in muscles, brain, skin and liver. Besides the almost universal presence of VDRs, some cell types (e.g. keratinocytes, monocytes, bone, placenta) are capable of metabolizing 25-hydroxyvitamin D3 to 1,25(OH)2D3 by the enzyme 1alpha-hydroxylase. The combined presence of 25(OH)D3-1alpha-hydroxylase as well as the specific receptor in severaltissues introduced the idea of a paracrine role for 1,25(OH)2D3. Moreover, it has been demonstrated that 1,25(OH)2D3 can inducedifferentiation and inhibit proliferation of normal and malignant cells. Besides the treatment of bone disorders with 1,25(OH)2D3, these newly discovered functions of 1,25(OH)2D3 open new therapeutic applications asan immune modulator (e.g. for the treatment of autoimmune diseases orprevention of graft rejection), inhibitor of cell proliferation (e.g. psoriasis) and inducer of cell differentiation (cancer).