Recent scientific discoveries that resulted from the application of next-generation DNA sequencing technologies highlight the striking impact of these massively parallel platforms on genetics. These new methods have expanded previously focused readouts from a variety of DNA preparation protocols to a genome-wide scale and have fine-tuned their resolution to single base precision. The sequencing of RNA also has transitioned and now includes full-length cDNA analyses, serial analysis of gene expression (SAGE)-based methods, and noncoding RNA discovery. Next-generation sequencing has also enabled novel applications such as the sequencing of ancient DNA samples, and has substantially widened the scope of metagenomic analysis of environmentally derived samples. Taken together, an astounding potential exists for these technologies to bring enormous change in genetic and biological research and to enhance our fundamental biological knowledge.