Certain crops were domesticated from their wild progenitors and have served as the major staple food since then, but now suffered from the limited genetic diversity in breeding. Enormous wild species possess unique advantages such as stress tolerance, polyploidy, perennial habit, and natural nutrition. However, it remains a big challenge to utilize wild species in conventional breeding. With recent advances in biotechnologies, one new breeding strategy, de novo domestication, has emerged and been demonstrated by pioneer work. Here, we review the emergence and milestone progress of de novo domestication and discuss how wild relatives could be exploited into new types of crops. With the understanding of the genetic basis of crop domestication and the development of biotechnologies, various elite wild germplasms will be designed and practiced to fulfill particular breeding goals and create new types of crops. De novo domestication is paving a new way for breeding the future.