Purpose of Review <p>Piriformis syndrome (PS) is an increasingly recognized cause of buttock pain and sciatica-like symptoms within the broader framework of deep gluteal syndrome. Injection-based minimally invasive treatments are commonly used when conservative therapy fails, yet reported outcomes remain heterogeneous. This structured narrative review with a systematic literature search evaluates the clinical effectiveness of local anesthetic, corticosteroid, and botulinum toxin injections for PS and examines the anatomical and procedural factors that may influence treatment response.</p> Recent Findings <p>Current evidence suggests that local anesthetic-based injection is particularly useful for rapid short-term pain relief and diagnostic clarification, whereas botulinum toxin may provide more sustained benefit in selected patients with persistent or recurrent symptoms. The additional role of corticosteroid appears less consistent and may depend on symptom mechanism and target selection. Anatomical variability in the relationship between the sciatic nerve and the piriformis muscle, differences in piriformis morphology, and variation in image-guided targeting appear to be major determinants of treatment outcome.</p> Summary <p>The effectiveness of injection-based treatment for PS should be interpreted within a framework that integrates pharmacologic action, anatomical variation, and procedural precision. A more anatomically informed and mechanism-based approach may improve patient selection, procedural accuracy, and overall clinical outcomes.</p>