The secosteroid hormone vitamin D, vitamin D receptor (VDR), and the metabolizing enzymes involved in the formation of the biologically active form of the hormone, acting together, are major players in the vitamin D endocrine system. This system plays an important role in skeletal metabolism, including intestinal calcium absorption, but has also been shown to play an important role in other metabolic pathways, such as those involved in the immune response and cancer. The interpretation of polymorphic variations in candidate genes of the vitamin D endocrine system (such as the VDR gene or the DBP gene) is severely hindered by the fact that, until recently, only few polymorphisms in these genes were studied. To understand the mechanisms underlying the associations, one has to analyze the genomic organization of the loci, to identify which genes are present in the chromosomal area, to categorize all relevant polymorphisms, to determine the linked alleles (or haplotypes) across the gene, to determine their relationship with the markers used so far, and, finally, to perform association analyses with relevant phenotypic endpoints such as disease.