Charles Darwin had based his theory of biological evolution on the observation that phenotypic variants of a given species can sometimes over-grow their parental population, and he attributed this to selective advantage, i.e., to the impact of natural selection. It later became obvious that stable, inheritable, phenotypic variants are spontaneous mutants with altered DNA sequences. Since a few decades one can explore the molecular mechanisms which generate genetic variants. Interestingly, many kinds of specific molecular mechanisms contribute to the overall generation of genetic variants. These mechanisms can be classified into three natural strategies of genetic variation: (1) Local changes in the nucleotide sequence, (2) intragenomic rearrangement of DNA segments, and (3) acquisition of a foreign DNA segment by horizontal gene transfer. These investigations revealed that a number of specific gene products acting as variation generators and/or as modulators of the rates of genetic variation are at work together with non-genetic elements, such as intrinsic physico-chemical properties of molecules, random encounter and environmental mutagens. In conclusion: Natural reality takes actively care of biological evolution. Philosophical and practical aspects of this acquired knowledge will be discussed.