PURPOSE OF REVIEW: Genomic and transcriptomic sequencing technologies have revolutionized our ability to characterize prostate cancer at the molecular level. The underlying premise of next-generation sequencing technologies and their current and evolving applications in prostate cancer management are provided in the review. RECENT FINDINGS: Improved methodologies are allowing timely sequencing of the coding regions or both the coding and noncoding regions of the genome to help identify potential mutations and structural variations in the prostate cancer genome, some of which are currently also targetable therapeutically. DNA microarray- based differential gene expression has been supplanted by RNA sequencing (RNA-seq), which not only allows for more accurate quantitation but also nucleotide-level resolution to investigate the entire transcriptome, including alternative gene spliced transcripts and noncoding RNA transcripts, whose full clinical implications have yet to be fully understood and realized. Gene classifier platforms that predict risk of recurrence or metastasis are being incorporated into prostate cancer management algorithms. In the appropriate clinical context, not only somatic but also germline mutation testing is being recommended. SUMMARY: Continued clinical integration of sequencing technologies and ongoing research will lead to improved understanding of prostate cancer biology and prostate cancer treatment.