The epithelial Ca(2+) channels TRPV5 and TRPV6 constitute the apical Ca(2+) entry mechanism in active Ca(2+) (re)absorption. These two members of the superfamily of transient receptor potential (TRP) channels were cloned from the vitamin-D-responsive epithelia of kidney and small intestine and subsequently identified in other tissues such as bone, pancreas and prostate. These channels are regulated by vitamin D as exemplified in animal models of vitamin-D-deficiency rickets. In addition, the epithelial Ca(2+) channels might be involved in the multifactorial pathogenesis of disorders ranging from idiopathic hypercalciuria, stone disease and postmenopausal osteoporosis. This review highlights the emerging (patho)physiological implications of these epithelial Ca(2+) channels.