Interleukin-1 (IL-1) is a multifunctional cytokine that regulates various cellular and tissue functions. Among tissues, bone is the most sensitive to IL-1. IL-1 is a potent cytokine for bone resorption and participates in the multiple steps of osteoclast recruitment, such as differentiation, multinucleation, activation, and survival. On the other hand, considerable evidence has been accumulated over the past 10 years to indicate that this cytokine plays key roles in pathological bone destruction in a variety of human diseases, including rheumatoid arthritis, osteoporosis, and periodontal disease. In this chapter, we review the history of "IL-1 in bone" and the locus of this cytokine "from laboratory bench to bedside." A better understanding of the role of IL-1 in osteoclastic bone resorption would provide opportunities for developing new therapeutics to treat diseases of the bone.