This paper addresses the genetic resources, domestication and breeding history of spinach as a comprehensive review of these crop aspects is currently unavailable. It is shown that the availability of genetic resources of wild relatives belonging to the primary gene pool is currently very limited, which hampers breeding and research activities. Therefore, new collecting expeditions are clearly warranted. The domestication of spinach is discussed on the basis of its presumed migration routes and the traits that were probably involved in the domestication syndrome. Spinach is thought to have domesticated in former Persia. Migration then occurred eastwards to China and westwards to Europe, but additional genetic data are needed to reveal the most likely migration routes. Morphological changes in pistillate flowers and loss of dormancy are identified as the main traits involved in the domestication syndrome of spinach. To a large extent we could re-construct the relationships between spinach cultivars that were developed until the 1950s, but this appeared difficult for the more recent cultivars due to intellectual property protection by breeding companies. Resistance against downy mildew has been the main breeding target in spinach. The introgression of NBS-LRR resistance genes from wild relatives is the major strategy to develop downy mildew resistant cultivars. However, the use of loss-of-function alleles of susceptibility genes may provide a more durable strategy to develop resistant cultivars. So far, abiotic resistance and quality traits have received minor attention in spinach research and breeding. This is expected to change considering the potential effects of climate change on these traits.