Genetic studies of calcium kidney stones have so far assessed single candidate genes by testing linkage disequilibrium or association between a locus and stone disease. They showed the possible involvement of the calciumsensing receptor gene, vitamin D receptor gene, and bicarbonate-sensitive adenylate cyclase gene. In addition to research in humans, the study of different strains of knock-out mice let us include the gene of phosphate reabsorption carrier NPT2, caveolin-1, protein NHERF-1 modulating calcium and urate reabsorption, osteopontin and Tamm-Horsfall protein among the possible determinants. However, the interactions between genes and also between environmental factors and genes are generally considered fundamental in calcium stone formation. Thus, the genetic studies carried out to date have not led to a significant growth of the knowledge about the causes of calcium kidney stones, even though they have allowed us to assess the size of the problem and define criteria to address it. Further knowledge of the causes of calcium stones may be obtained using the instruments that modern biotechnology and bioinformatics have made available to researchers.