Interferons (IFNs) play essential roles in regulating osteoclast differentiation and bone resorption. Over the last decade, we have seen tremendous developments in our understanding of the mechanisms by which interferons regulate osteoclastogenesis. Of the type I interferons, IFN-β inhibits osteoclastogenesis via autoregulatory or exogenous regulatory mechanisms, while IFN-α was recently shown to participate in regulating osteoclast formation. And the only member of type II interferons, IFN-γ, has biphasic effects on osteoclastogenesis. Type III interferons have also been shown to be involved in osteoclast bone resorption, although no direct regulatory mechanism has been demonstrated. In this review, we provide an update account of the current knowledge on these recently revealed novel roles of interferons in the regulation of a variety of signaling pathways in osteoclast differentiation and function. The potential clinical applications are also discussed.