The invention and application of Next-Generation Sequencing (NGS) technologies have revolutionized the study of genetics and genomics. Much research which would not even be considered are nowdays being excuted in many laboratories as routine. In this chapter, we introduce the currently available NGS platforms, comparing their working theories and reveiwing their advantages and disavantages. We also discuss the future of NGS development and point out that single molecular sequencing would push the technology to the next level for biological sciences. Much of the chapter focuses on the use of NGS technologies in sorghum. Although the acquisition of the first whole-genome sequence in sorghum was carried out primarily using Sanger sequencing, the use of NGS for examining the genome-wide variation was almost synchronized with other work. Interesting genomic variation was found between sweet and grain sorghum. NGS has also been used to examine the transcriptomes of sorghum under various stress conditions. Besides identifying interesting transcriptonal adpatation to stress conditions, these study show that sugar could potentially act as an osmitic adjusting factor via transcriptional regulation. Furthermore, miRNAs are found to be important adaptation to both biotic and abiotic stresses in sorghum. We discuss the use of NGS for further genetic improvement and breeding in sorghum.