Mechanisms of chromosomal change, distribution patterns, extent of genotypic, phenotypic and ecological divergence, and nature and degree of reproductive isolation were reviewed in 10 chromosomally variable southern African rodent species and species complexes. Genetically similar peripatric or parapatric chromosome races freely interbreed (striped mice, Rhabdomys pumilio; vlei rats, Otomys irroratus), while genotypically or phenotypically divergent, sympatric sibling species (multimammate mice, Mastomys natalensis–M. coucha; tree rats, Thallomys paedulcus–T. nigricauda; red veld rats, Aethomys chrysophilus–A. ineptus) appear reproductively isolated, suggesting a correlation between genetic distance and onset of reproductive isolation. The allopatric gerbil species pair, Tatera brantsii–T. afra, shows little or no prezygotic reproductive isolation despite well-developed male-biased postzygotic isolation (i.e., Haldane effect) that may be associated with a rearrangement on the Y chromosome. Within the actively speciating vlei rat, Otomys irroratus, complex, despite widespread laboratory interbreeding between chromosome races, postzygotic isolation (virtual hybrid sterility) was demonstrated due to fixation of a tandem fusion rearrangement in the high-altitude (>1,400 m) A1 race. Both post- and prezygotic isolation have developed in the absence of significant measurable genotypic divergence at either the gene or the DNA level. Acquisition of reproductive isolation and incipient speciation in the vlei rat complex appears to be mediated by both chromosomal (postzygotic) and nonchromosomal (prezygotic) processes.