The technology to simultaneously genotype hundreds of thousands of single nucleotide polymorphisms in a single assay has only recently been developed. These advances have the potential to revolutionize our ability to identify disease-associated proteins and their corresponding pathways as drugable targets. Several strategies that can take advantage of extremely high-density, genome-wide single nucleotide polymorphism genotyping to hone in on pathogenic genetic variants will be discussed. In familial linkage studies, high-density single nucleotide polymorphism genotyping has already been proven to speed up mutation identification of Mendelian traits several fold. Many studies now report examining loss of heterozygosity and genomic amplifications on a whole-genome level. Genotyping hundreds of thousands of single nucleotide polymorphisms in a single set of assays now also allows for whole-genome association studies in complex, multigenic diseases. The technology of high-density single nucleotide polymorphism genotyping has emerged rapidly, leaving data analysis and bioinformatic challenges only partially met. In this review, the immediate applications and implications of the rapidly changing high-density, whole-genome single nucleotide polymorphism genotyping field on translational research will be described.