Evidence for a cancer preventive role for vitamin D has been accumulating since the early 1980s, most signifi cantly in blood, breast, and, most notably, colon cancers. Although vitamin D and its metabolites modulate proliferation, angiogenesis, differentiation, and apoptosis, their major function is to maintain calcium homeostasis. Thus, treatment with vitamin D may cause an imbalance of calcium, manifesting in clinical disorders such as hypercalcemia and hypercalciuria. To circumvent these side effects, two branches of research have evolved. The first aims to understand the molecular targets that contribute to the anticancer properties of vitamin D; the second aims to develop vitamin D analogues that retain anticancer properties but have diminished hypercalcemic properties. The purpose of this article is to review the literature regarding failures and successes of vitamin D analogues in colon cancer research.