All plant and animal species arise by speciation - the evolutionary splitting of one species into two reproductively incompatible species. But until recently our understanding of the molecular genetic details of speciation was slow in coming and largely limited to Drosophila species. Here, I review progress in determining the molecular identities and evolutionary histories of several new 'speciation genes' that cause hybrid dysfunction between species of yeast, flies, mice and plants. The new work suggests that, surprisingly, the first steps in the evolution of hybrid dysfunction are not necessarily adaptive.