Mutator and antimutator mutations arise continuously in all organisms from riboviruses to humans. They affect rates of both spontaneous and induced mutations and thus can affect evolutionary processes, the frequency of heritable genetic diseases, and diseases with origins in somatic mutation. Alternatively, both upregulation and down-regulation of mutation rates can occur as cells shuttle between stressful and benign environments, and long tenure in certain environments can drive adjustments in the normal rate of spontaneous mutation. Moreover, cells can experience unregulated bouts of transient hyper-mutation that can affect both evolution and mutation-driven disease. The stress responses increase mutagenesis specifically when cells are maladapted to their environments. The level of genetic variability that maximizes the fitness of a population varies with the degree of its adaptation to the environment. Evolution of bacterial populations may happen through alternating periods of high and low mutation rates. These provide a remarkable potential for the tuning of the rates of generations of genetic variability in the function of adaptation to environmental conditions. Organisms mutate and selection takes place, followed by lowering of mutation rates by antimutator activity, when niches are filled and organism are at equilibrium. Cancers are driven by mutator genes. Are the extremely rare, spontaneous, complete cancer remissions responding to antimutator activity?