Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system allows biologists to edit genomic DNA of any cell in precise and specific way, entailing great potential for crop improvement, drug development and gene therapy. The system involves a nuclease (Cas9) and a designed guide RNA that are involved in wide range of applications such as genome modification, transcriptional modulation, genomic loci marking and RNA tracking. The limitation of the technique, in view of resistance of thymidine-rich genome to Cas9 cleavage, has now been overcome by the use of Cpf1 nuclease. In this review, we present an overview of CRISPR nucleases (Cas9 or Cpf1) with particular emphasis on human genome modification and compare their advantages and limitations. Furthermore, we summarize some of the pros and cons of CRISPR technology particularly in human therapeutics.