Musculoskeletal pain is a challenging condition for both patients and physicians. Many adults have experienced one or more episodes of musculoskeletal pain at some time of their lives, regardless of age, gender, or economic status. It affects approximately 47% of the general population. Of those, about 39-45% have long-lasting problems that require medical consultation. Inadequately managed musculoskeletal pain can adversely affect quality of life and impose significant socioeconomic problems. This manuscript presents a comprehensive review of the management of chronic musculoskeletal pain. It briefly explores the background, classifications, patient assessments, and different tools for management according to the recently available evidence. Multimodal analgesia and multidisciplinary approaches are fundamental elements of effective management of musculoskeletal pain. Both pharmacological, non-pharmacological, as well as interventional pain therapy are important to enhance patient's recovery, well-being, and improve quality of life. Accordingly, recent guidelines recommend the implementation of preventative strategies and physical tools first to minimize the use of medications. In patients who have had an inadequate response to pharmacotherapy, the proper use of interventional pain therapy and the other alternative techniques are vital for safe and effective management of chronic pain patients.