In the evolving field of orthopedics, the shift towards personalized medicine heralds a new era of patient care-promising enhanced treatment accuracy and improved outcomes. This collection, derived from the Special Issue in the Journal of Personalized Medicine, showcases cutting-edge research and reviews focusing on tailoring orthopedic treatments to individual patient needs. Emphasizing innovation in surgical technologies, implant designs, and non-operative approaches, this SI critically addresses the challenges of standardization and the necessity for patient-specific treatment strategies. Contributions delve into understanding the diverse responses to orthopedic treatments, exploring patient-specific disease mechanisms, and the potential for personalized therapeutic regimens to optimize clinical results and minimize complications. This reprint aims to inspire a future where orthopedic medicine not only addresses the disease, but also reflects the unique health blueprint of each patient. We thank our contributors for their insightful research, pushing the boundaries towards a personalized approach in orthopedic care.