This review summarizes the overall downstream applications of currently available genome customization systems, based on cell-based assays (in cellulo) or animal models (in vivo). These include (i) functional genomics, (ii) drug discovery, (iii) bioprodn., (iv) cell transformation (i.e. immortalization, reprogrammation and differentiation), as well as (v) mol. biol. and microbiol. tools. The different enzymic systems that exist to specifically modify (insertional or site-directed mutagenesis), modulate (knock-down) and disrupt (constitutive or conditional knock-out) cellular genes, or to integrate transgenic elements (knock-in) at specific chromosomal loci are discussed.