Bone remodeling is essential for adult bone homeostasis. The failure of this process often leads to the development of osteoporosis, a present major global health concern. The most important factor that affects normal bone remodeling is the tightly controlled and orchestrated regulation of osteoblasts and osteoclasts. The present review summarized the recent discoveries related to osteoblast regulation from several signals, including transforming growth factor-β, bone morphogenetic proteins, Wnt signal, Notch, Eph–Ephrin interaction, parathyroid hormone/parathyroid hormone-related peptide, and the leptin–serotonin–sympathetic nervous systemic pathway. The awareness of these mechanisms will facilitate further research that explores bone remodeling and osteoporosis. Future investigations on the endogenous regulation of osteoblastogenesis will increase the current knowledge required for the development of potential drug targets in the treatment of osteoporosis.