The sequencing of the human genome, combined with brilliant technical advances in microarrays and computing, opened the genomic era of personalized medicine. The next generation of genomics is now being driven by massively parallel sequencers that are effectively high definition genetic analyzers capable of sequencing an entire human genome 30-times over in approximately a week for several thousand US dollars. Likewise, these next-generation sequencers, sometimes called deep sequencers, can sequence RNA transcriptomes to render unprecedented, high definition views of transcript sequence, SNP haplotypes, rare variants, splicing, exon boundaries and RNA editing. Presently, next-generation sequencing platforms can be grouped into 'discovery' platforms, which provide broad sequence coverage, but require days per sample, versus 'diagnostic' platforms, which provide a fraction of the coverage, but require only hours for sequencing. As these technologies converge, it will be possible to sequence a human genome in a matter of hours for a few hundred US dollars. While presenting considerable technical challenges in handling the massive data generated, next-generation sequencing platforms offer unparalleled opportunities for biological insights, target discovery and clinical diagnostics to accelerate personalized medicine in the coming years.