Histone acetylation orchestrates a complex symphony of gene expression that controls cellular fate and activities, including the intricate processes of bone remodeling. Despite its proven significance, a systematic illustration of this process has been lacking due to its complexity, impeding clinical application. In this review, we delve into the central regulators of histone acetylation, unveiling their multifaceted roles in modulating bone physiology. We explore both contradictory and overlapping roles among these regulators and assess their potential as therapeutic targets for various bone disorders. Furthermore, we highlight current applications and discuss looming questions for a more effective use of epigenetic therapy in bone diseases, aiming to address gaps in knowledge and clinical practice. By providing a panoramic view of histone acetylation's impact on bone health and disease, this review unveils promising avenues for therapeutic intervention and enhances our understanding of skeletal physiology, crucial for improving therapeutical outcomes and quality of patients' life.