Apple breeding has been extremely successful in providing a highly diverse fruit crop. Recent (>50 millions years ago) genome-wide duplication (GWD) resulted in the 17 chromosomes in the Pyreae (Velasco et al. 2010) and confirmed the origin of cultivated apple on Malus sieversii being the same species as M. × domestica. Malus, as many other species in the family Rosaceae, shows gametophytic self-incompatibility (GSI), which forces outcrossing. GSI at the pistil is regulated by extacellular ribonuclease, S-RNase, which is encoded by S locus. Growers and agronomists have provided multiple cultivars with different colors, shapes, resistances, climatic adaptation or industrial aptitudes. The aim in apple breeding was the combination of different kinds of resistance and good fruit quality to produce dessert cultivars and cultivars for processing. Some of the best of these cultivars display resistance to scab (Venturia inaequalis), mildew (Podosphaera leucotricha), fire blight (Erwinia amylovora), bacterial canker (Pseudomonas syringae), red spider mite (Panonychus ulmi), winterfrost and good fruit quality. Different scab resistance sources of wild species (Vf, Vr, VA) were combined in the new series of cultivars. Multiple efforts worldwide have conserved most of that variation, the pillar for the traditional and new techniques profiting from the analysis of the apple genome, the genome-wide association studies (GWAS), identifying SNPs and genes, the analysis of genes differentially expressed (GDE) identified by qRT-PCR and microarray analysis, and the recent molecular genetic tool CRISPR/Cas9 to edit and correct the genome.