Comparative (meta)genomics have made us realize that horizontal evolutionary phenomena have been vastly underestimated. The serial endosymbiogenetic theory has proven the symbiogenetic origin of mitochondria and plastids. Symbiosis studies further prove that symbiotic unions continue to be relevant to understand evolution. Symbiotic unions can become transmitted vertically, from parent to offspring, through means other than germ-line transmission. Abundant evidence also exists for horizontal or lateral gene transfer in microorganisms. And evidence is piling up that lateral gene transfer also occurs abundantly in eukaryotic organisms. Gene sequencing techniques further prove that viruses also contribute to the evolution of life. They may have played a crucial role in the development of the genetic code, and viral genes are abundantly present in non-coding DNA regions that used to be designated as “junk DNA.” Such horizontal evolutionary phenomena pose major challenges to the Modern Synthesis, which makes a clear distinction between ontogeny and phylogeny, emphasizes germ-line transmission, and defines speciation as a splitting or “branching off” process. Horizontal evolutionary studies have consequences for how we define units of evolution, and biological individuals, how we draw the tree of life, and how we conceptualize speciation.