Selfing has evolved in animals, fungi, and plants, and since Darwin’s pioneering study, it is considered one of the most frequent evolutionary trends in flowering plants. Generally, the evolution of selfing is characterized by a loss of self-incompatibility, the selfing syndrome, and changes in genome-wide polymorphism patterns. Recent interdisciplinary studies involving molecular functional experiments, genome-wide data, experimental evolution, and evolutionary ecology using Arabidopsis thaliana, Caenorhabditis elegans, and other species show that the evolution of selfing is not merely a degradation of outcrossing traits but a model for studying the recurrent patterns underlying adaptive molecular evolution. For example, in wild Arabidopsis relatives, self-compatibility evolved from mutations in the male specificity gene, S-LOCUS CYSTEINE-RICH PROTEIN/S-LOCUS PROTEIN 11 (SCR/SP11), rather than the female specificity gene, S-LOCUS RECEPTOR KINASE (SRK), supporting the theoretical prediction of sexual asymmetry. Prevalence of dominant self-compatible mutations is consistent with Haldane’s sieve, which acts against recessive adaptive mutations. Time estimates based on genome-wide polymorphisms and self-incompatibility genes generally support the recent origin of selfing.