For some time, the reversibility of evolution was primarily discussed in te
rms of comparative patterns. Only recently has this problem been studied us
ing experimental evolution over shorter evolutionary time frames. This has
raised questions of definition, experimental procedure, and the hypotheses
being tested. Experimental evolution has provided evidence for multiple pop
ulation genetic mechanisms in reverse evolution, including pleiotropy and m
utation accumulation. It has also pointed to genetic factors that might pre
vent reverse evolution, such as a lack of genetic variability, epistasis, a
nd differential genotype-by-environment interactions. The main focus of thi
s perspective is on laboratory studies and their relevance to the genetics
of reverse evolution. We discuss reverse evolution experiments with Drosoph
ila, bacterial, and viral populations. Field studies of the reverse evoluti
on of melanism in the peppered moth are also reviewed.