A CRISPR-Cas system is an extensively studied defense mechanism that protects bacteria and archaea against invading bacteriophage and plasmids. Currently, it is being used for editing the genome in many organisms. CRISPR-Cas system is a key genome editing technology which is simple, cost-effective, specific and user-friendly. It requires the expression of Cas9 endonuclease, single guide RNA and PAM sequence. The Cas9-sgRNA complex binds and creates a double-stranded break (DSB)that is repaired by non-homologous end joining (NHEJ)or by the homology-directed repair (HDR)pathway. This allows the generation of indels, which in turn allows modification of target DNA sequences. More recently, a number of Cas versions have been discovered and developed for gene editing, imaging of genomic loci, gene regulation, diagnostics and many more. In this chapter, we highlight the recent progress, use and challenges of the CRISPR platform for a wide range of therapeutic and biotechnological applications.