Osteoclasts (OC), traditionally regarded as the primary cells responsible for bone resorption, are essential for skeletal remodeling, mineral homeostasis, and structural integrity. Studies have shown that OC actively participate in bone regeneration by interacting with osteoblasts (OB), mesenchymal stem cells (MSC), and immune cells to coordinate bone resorption and formation. This chapter focuses on exploring the dual functions of OC in bone health, starting with an analysis of their origin, differentiation, and the molecular mechanisms involved in bone resorption. It then investigates the signaling pathways and coupling factors, such as TGF-β, BMPs, and IGFs, that connect OC-mediated resorption to subsequent OB-driven bone formation. Additionally, the interactions between OC and immune cells within the bone microenvironment and age-related changes in OC activity are examined to highlight OC’s roles in various pathological conditions, including osteoporosis, arthritis, and bone metastasis. Emerging therapeutic approaches, such as anti-resorptive drugs, combination therapies, and novel treatments designed to modulate OC function to enhance regeneration while avoiding inhibition of bone resorption, are also discussed. The potential for personalized medicine using biomarkers, gene editing, and pharmacogenomic strategies is further emphasized as a promising direction for optimizing treatment efficacy and safety. By shedding light on the multifaceted roles of OC, this chapter highlights their significance in maintaining bone homeostasis and provides insights for the development of innovative therapies that balance resorptive and regenerative functions, ultimately improving outcomes for patients with bone-related diseases.