This review, with the help of a case study, provides a detailed account of the possible biopsychosocial risk factors underlying piriformis muscle syndrome, post discectomy. The diagnostic process including imaging, nerve conduction studies, musculoskeletal examination coupled with provocation maneuvers, palpation, and the musculoskeletal differential diagnosis of buttock pain is illustrated. Reference is made to the aberrant sciatic nerve anatomy and to the myofascial component which is frequently reported to underlie piriformis muscle syndrome. Additionally, the use of validated neuropathic pain assessment tools in grading the possibility of neuropathic pain due to piriformis muscle syndrome is discussed. The prevalence and mechanisms of piriformis muscle syndrome, especially post sipnal surgery, are reviewed. Evidence-based multidisciplinary management underlying this condition is discussed. In refractory cases, treatment escalation, using intramuscular botulinum neurotoxin injection, usually yields very positive results and long-term pain resolution, as evidenced by the case study.