Identification of genes that harbor variation associated with inter-individual differences in risk of complex diseases remains one of the most challenging and important problems in human genetics. For genetic variants that are sufficiently common and have sufficiently large effects, direct tests of association through linkage disequilibrium with anonymous SNPs may prove effective. But the two critical parameters - the frequency of risk-inflating alleles and the magnitudes of their effect on risk - remain largely unknown. In this review we consider the latest information regarding the likely efficacy of the linkage disequilibrium mapping approach.