Mobile genetic elements drive bacterial evolution, while exposing bacteria to the risk of invasion by “selfish genes”. In the arms race with mobile genetic elements, bacteria have evolved a range of immune systems that can protect hosts from invading nucleic acids. These immune systems are capable of preventing the invasion of mobile genetic elements, degrading invading nucleic acids, inhibiting the replication or transcription of invading nucleic acids, or inducing abortive infections to protect the population. Although much is known about the working mechanisms of these host immune systems, it remains unclear how bacteria orchestrate different defense strategies in response to different stages of nucleic acid invasion. Based on our research and different immune strategies of bacteria to limit mobile genetic elements in different spatiotemporal dimensions, this review summarizes and classifies the host immune systems. The elucidation of these multilayered immune mechanisms not only reveals the arms race between host and mobile gene elements in the evolutionary process but also underpins the development of new biotechnologies.