Mesenchymal cells of the sea urchin embryo provide a valuable experimental model for the analysis of cell-cell fusion in vivo. The unsurpassed optical transparency of the sea urchin embryo facilitates analysis of cell fusion in vivo using fluorescent markers and time-lapse three-dimensional imaging. Two populations of mesodermal cells engage in homotypic cell-cell fusion during gastrulation: primary mesenchyme cells and blastocoelar cells. In this chapter, we describe methods for studying the dynamics of cell fusion in living embryos. These methods have been used to analyze the fusion of primary mesenchyme cells and are also applicable to blastocoelar cell fusion. Although the molecular basis of cell fusion in the sea urchin has not been investigated, tools have recently become available that highlight the potential of this experimental model for integrating dynamic morphogenetic behaviors with underlying molecular mechanisms.</p