The CRISPR technology has recently received extensive attention from the research and medical community due to its remarkable genome-editing capacity. In particular, the therapeutic potential of translating the CRISPR technology into clinical interventions for various human diseases has brought bright hopes for patients around the world. In the current Commentary, I shall scrutinize recent advances in manipulating and improving the CRISPR technology for viral diseases and genetic disorders in humans. Key challenges to realize the full clinical potential of the CRISPR technology will also be discussed.