Over the years there have been many different approaches and techniques that have been utilized to gather genetic information on family and patient data. Early on these focused on using family information and the pattern of inheritance of the disease in the family. The general location of the disease gene on the chromosomes could be determined using linkage analysis. But this required large families and good family histories. Association studies moved away from family data, but still required large numbers of patients sharing the same disease. Over the past several decades we have had continuing growth in the number of genetic “markers” that we could use in linkage and association analyses, the most recent work utilizing the specific sequence changes called single nucleotide polymorphisms or SNPs. But the use of these markers did not eliminate the need for large families or large population sizes. Thus, despite advances in genotyping technology, the parameters of the applications in which these techniques could be used have not changed much in 30 years or so. This prevented many of the most interesting cases and families with Mendelian inheritance (due to a mutation in a single gene) from being studied, as they were too small for analysis, or too rare. Sequencing genes provided more information, but the previous existing technology was too expensive and labor intensive to do a large number of genes. Thus investigators were dependent on choosing candidate genes for study, which historically has proven to be fairly inefficient. But this paradigm of needing large families to investigate a disease, or choosing a few candidate genes to test a hypothesis is now changing. The rapidly emerging sequencing technology has now allowed the first practical medical application of the most useful and enlightening measure of genetic information, the DNA sequence itself. The output of sequencing has been increasing at a rapid pace over the past several years, passing even the growth of the computer chip made famous by “Moore’s law” (Moore, G. E. 1965). During the 1990’s and early in this century, capillary sequencers, which produced the data for the human genome project, could identify 500 to 1,000 base pairs of sequence at a time. While impressive relative to previous slab gel techniques, the Next Generation Sequencers (NGS) of today have increased that sequencing output a million fold or more (Fig. 1). This also means that the cost of sequencing per base pair has dropped precipitously. The human genome is approximately 3.4 billion base pairs. The cost of sequencing was approximately 10 million dollars in 2003. This dropped to around a million dollars in 2007, less than a $100,000 by 2009, and is expected to be close to the $1,000 goal in 2011-2012. How has this remarkable increase been accomplished? Sanger sequencing has been the mainstay of sequencing for many years. The Sanger sequencing method that was used for the human genome project utilizes a small primer (usually 20 base pairs) , that allows the sequencing reaction to