Osteoclasts are unique cells that degrade the bone matrix. These large multinucleatedcells differentiate from the monocyte/macrophage lineage upon stimulation by two es-sential cytokines, macrophage colony-stimulating factor (M-CSF) and receptor activatorof nuclear factor-kappa B (NF-κB) ligand (RANKL). Activation of transcription factors suchas microphthalmia transcription factor (MITF), c-Fos, NF-κB, and nuclear factor-activatedT cells c1 (NFATc1) is required for sufficient osteoclast differentiation. In particular, NFATc1plays the role of a master transcription regulator of osteoclast differentiation. To date,several mechanisms, including transcription, methylation, ubiquitination, acetylation,and non-coding RNAs, have been shown to regulate expression and activation of NFATc1. In this review, we have summarized the various mechanisms that control NFATc1 regula-tion during osteoclast differentiation.