Recent advances in genome engineering indicate that innovative crops developed by targeted genome modification (TGM) using site-specific nucleases (SSNs) have the potential to avoid the regulatory issues raised by genetically modified organisms. These powerful SSNs tools, comprising zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regulatory interspaced short palindromic repeats/CRISPR-associated systems, enable precise genome engineering by introducing DNA double-strand breaks that subsequently trigger DNA repair pathways involving either non-homologous end-joining or homologous recombination. Here, we review developments in genome-editing tools, summarize their applications in crop organisms, and discuss future prospects. We also highlight the ability of these tools to create non-transgenic TGM plants for next-generation crop breeding.