Learning and memory is a delicate process of acquiring, storing and reconsolidating the knowledge with a behavioral output, which is indispensable for animals to adapt to their living environment. Defects in learning and memory contribute to some psychiatric disorders such as schizophrenia, depression and Alzheimer’s disease, and are recently reported to be inheritable from the parental generation to their offspring. However, it is not clear currently what the mechanism is underlying the learning and memory inheritance due to the lack of animal models. In this perspective type of mini-review, we first briefly summarize the current understanding of the molecular basis, neural circuit and transgenerational inheritance of learning and memory. We then focus on discussing the possibility of using Drosophila as an animal model to study the transgenerational inheritance of learning and memory and propose potential strategies to achieve the goal.