The innate immune system is old, conservative and important anti-infection defense system. How does the innate immune system defend against an array of invading microbial pathogens including bacteria, viruses, parasites and fungi, which becomes an important research topic in the immunological fields. This article just summarized the different stages of immune defense against pathogenic microorganism, including the innate immune recognition, the recruitment of innate immune cells, and the pathogen immune clearance.