Under physiological conditions, programmed cell fusion occurs during fertilization, embryonic development, tissue and organ formation, and colony formation. Cell fusion also occurs under pathologic conditions such as inflammation, cancer, and pathogen infection. Various animal and plant pathogens, such as viruses, bacteria, and parasitic nematodes, induce cell fusion to facilitate spred, evade the host immune response, or serve as nutrient source. In this short review, we discuss various examples and underlying mechanisms of pathogen-mediated cell fusion, emphasizing the role of the actin cytoskeleton and the actin nucleation pathway in the pathogen life cycle and the fusion processes.