It is now possible to modify the genome with spatial and nucleotide precision using genome editing.This has been made possible through the concerted efforts of a wide range of researchers with the integration of exciting discoveries from diverse fields.In this presentation I will discuss the range of different specific genome modifications that can be generated using both nuclease and non-nuclease mediated approaches.These precise modifications can be generated by harnessing the cells own endogenous DNA double-strand break repair pathways including non-homologous end-joining and homologous recombination.Moreover, there are now a number of different engineered nuclease platforms that can be utilized for precisely modifying the genome including the use of modified homing endonucleases, zinc finger nucleases, TAL effector nucleases,RNA guided endonucleases of the CRISPR/Cas9 family, and mega-TAL nucleases.The advantages and disadvantages of each of these different nuclease platforms will be discussed.In sum, there is tremendous potential in using genome editing to develop novel therapeutics for human disease and the promise and challenges of fulfilling this potential will be discussed.