Chromosomes are commonly regarded as conservative structures, in which an exact amount of genetic information is arranged in a definite sequential order. This order is normally preserved when information is exchanged between chromosomes, and guaranteed by a set of recombination enzymes that function only with paired sectors of homologous DNA. But processes such as inversion, deletion, duplication and translocation, often involving recombination between apparently non-homologous chromosomal regions, can alter this sequential order. Chromosomal rearrangements resulting from such events have been observed, in some cases with a disturbingly high frequency, thus inviting speculation about their biological significance. The processes involved have been termed collectively “illegitimate recombination”, reflecting our bias for conventional pathways based on sequence homology, but evidence is accumulating which may legitimatize them as important aspects of evolution or even differentiation.