Sweet cherry (Prunus avium L.) world production has been steadily increasing in the last decades. Accordingly, breeders are releasing new cultivars at an unprecedented pace, in order to meet growers and consumers demands. However, new challenges are faced in sweet cherry cultivation, in particular regarding abiotic and biotic stresses related to climate change and to invasive pests or emerging diseases, respectively. There is a growing demand for new cultivars which combine high fruit quality and adaptation to these environmental constraints. As sweet cherry breeding is a long process, modern scientific tools and methodologies are needed to accelerate the progress and optimize selection schemes. A promising field of research and application was opened a few decades ago with the advent of molecular biology techniques which enabled the exploration of variability at the DNA, or genomic level. The generation of genomic tags, called molecular markers, allowed the characterization of genetic resources and the study of the genetic determinism of the main agronomic traits of interest. Since then, strategies to use this information in breeding have been developed, called marker-assisted breeding or, more generally, DNA-informed breeding. The objectives of this review are: (i) to recall the main scientific achievements in the fields of genetics in sweet cherry that could be directly beneficial for breeders, (ii) to summarize the practical steps needed to implement DNA-informed breeding and to illustrate several strategies adopted by sweet cherry breeders and (iii) to open new perspectives for a more efficient integration of these methodologies in breeding programs.