Microorganisms like bacteria, archaea, fungi, microalgae, and viruses mostly form complex interactive networks within the ecosystem rather than existing as single planktonic cells. Interactions among microorganisms occur between the same species, with different species, or even among entirely different genera, families, or even domains. These interactions occur after environmental sensing, followed by converting those signals to molecular and genetic information, including many mechanisms and classes of molecules. Comprehensive studies on microbial interactions disclose key strategies of microbes to colonize and establish in a variety of different environments. Knowledge of the mechanisms involved in microbial interactions is essential to understand the ecological impact of microbes and the development of dysbioses. Furthermore, it might be the key to exploit strategies and specific agents against different facing challenges, such as chronic and infectious diseases, hunger crisis, pollution, and sustainability.