<p>The sciatic nerve, the largest peripheral nerve in the human body, demonstrates anatomical variability in its course, bifurcation level, and relationship with the piriformis muscle. These variations are clinically significant because they can affect diagnostic accuracy, surgical intervention, nerve block efficacy, and interpretation of radiological findings. This review aims to review current knowledge regarding the anatomical variations of the sciatic nerve; their reported prevalence across cadaveric, radiological, and surgical studies; and the implications of these findings for clinical practices. The Beaton and Anson classification system served as the primary framework, with additional categorization for unclassified and complex variants. The most commonly observed sciatic nerve configuration is Type A, where the undivided nerve exits below the piriformis muscle, with prevalence ranging from 76% to over 90%. Type B, in which the common peroneal nerve pierces the piriformis muscle, is the next most frequent variant, with reported prevalence of up to 24.8% of adult cases. High and low bifurcations of the sciatic nerve have also been frequently documented. These anatomical variations have been linked to increased risk of piriformis syndrome, unsuccessful sciatic nerve blocks, and iatrogenic injury during total hip arthroplasty and other deep gluteal surgeries. Recognition of sciatic nerve variants is essential for clinicians, particularly in orthopedics, anesthesiology, and radiology. Preoperative imaging with MRI or ultrasound can enhance diagnostic accuracy and reduce complications. Future research should focus on standardizing the variant classification system and expanding anatomical data across diverse populations to improve surgical planning and clinical applications.</p>