Syncytia are multinucleated cells created by fusion of normal cells. Some viruses are known to induce syncytia formation as a consequence of infected cells expressing viral surface proteins. The role of syncytia in the spread of viral infections and the resulting disease is still poorly understood. Researchers have developed cell-cell fusion assays to help study the fusion process. These assays use cells transfected to express viral surface proteins to study the fusion process without an active viral infection. Recently, mathematical models have been developed to simulate the dynamics of these assays and have been used to estimate parameters that characterize the fusion process. This review examines the cell-cell fusion assay and the mathematical models that have been developed to reproduce assay dynamics. While modeling of these systems is still in its early stages, further extension of these models will help improve our understanding of the syncytia formation process.