Abstract: Focal segmental glomerulosclerosis (FSGS) is a refractory kidney disease that poses substantial clinical challenges. FSGS is primarily characterized by proteinuria and progressive loss of renal function. Its pathogenesis is complex and varied, involving immune-mediated injury, podocyte dysfunction, genetic factors, and changes in renal hemodynamics. According to pathologic features and etiology, FSGS can be classified into primary, hereditary, secondary, and undetermined-cause forms. Existing therapeutic strategies are mostly based on specific disease classifications and include the administration of hormones and drugs such as immunosuppressants, angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs). For drug-induced FSGS, the key measure is to discontinue the causative drug. On the other hand, for cases caused by hypertension and other factors, controlling blood pressure is a critical component of treatment. However, the effectiveness of current therapeutic strategies remains variable, and the relatively high rates of adverse effects and recurrence underscore the fact that they do not fully meet the clinical needs. Therefore, in-depth exploration and optimization of FSGS treatment strategies, along with the development of novel drugs with enhanced therapeutic efficacy and reduced risks of adverse effects and recurrence, have become the core direction of current renal disease research. With a deeper understanding of the pathogenesis of FSGS, new approaches such as immunomodulation, podocytoprotection, and genetic targeted interventions are emerging, which is expected to promote innovation in treatment modalities and improve prognosis and quality of life for patients. Against this background, this article reviews the status of existing treatments and outlines future directions for research and clinical practice, providing both theoretical basis and practical guidance for exploration in this field.