To fully understand the allelic variation that underlies common diseases, complete genome sequencing for many individuals with and without disease is required. This is still not technically feasible. However, recently it has become possible to carry out partial surveys of the genome by genotyping large numbers of common SNPs in genome-wide association studies. Here, we outline the main factors — including models of the allelic architecture of common diseases, sample size, map density and sample-collection biases — that need to be taken into account in order to optimize the cost efficiency of identifying genuine disease-susceptibility loci.