Microbes have co-evolved with human beings for millions of years. They play a very important role in maintaining the health of the host. With the advancement in next generation sequencing technology, the microbiome profiling in the host can be obtained under different circumstances. This review focuses on the current knowledge of the alteration of complex microbial communities upon the infection of different pathogens, such as human immunodeficiency virus, hepatitis B virus, influenza virus, and Mycobacterium tuberculosis, at different body sites. It is believed that the increased understanding of the correlation between infectious disease and the alteration of the microbiome can contribute to better management of disease progression in the future. However, future studies may need to be more integrative so as to establish the exact causality of diseases by analyzing the correlation between microorganisms within the human host and the pathogenesis of infectious diseases.