Multinucleated osteoclasts, generated by fusion of mononucleated precursors, play an essential role in the lifelong remodeling of our bones. Since within the physiological range of osteoclast sizes, their bone-resorbing activity grows with successive fusion events, both initiation of this fusion reaction and its switch off are tightly controlled. In this review, we discuss the mechanisms and proteins that facilitate and regulate this fusion process. The pathway of membrane rearrangements in osteoclast fusion shares many mechanistic motifs with other physiologically important cell–cell fusion processes, such as the formation of multinucleated skeletal muscle cells. However, the protein machinery involved in catalyzing these rearrangements in osteoclasts is still poorly understood. A better understanding of the mechanism of osteoclast fusion will hopefully lead to more effective approaches for treating skeletal diseases caused by excessive or insufficient bone resorption.