Focal segmental glomerulosclerosis (FSGS) is the primary renal disease in approximately one-tenth of pediatric patients receiving a renal allograft. Recurrence of proteinuria after renal transplantation is observed in approximately 30% of patients and negatively impacts graft survival. Risk factors for recurrence are a chronological age <15 years at onset of the nephrotic syndrome and a rapid progression of the disease in the native kidneys leading to end-stage renal disease in less than 3 years. Mesangial proliferation in the native kidneys is also an important negative predictive factor for disease recurrence. With rapid recurrence of FSGS and loss of the allograft, further renal transplants also carry a high likelihood of FSGS recurrence. Different pathogenic factors have been discussed for the recurrence of proteinuria/FSGS in the transplanted kidney, especially the involvement of a proteinuric circulating factor, whose production seems to follow T-cell dysfunction. In the last decade, mutations in genes encoding podocyte proteins have been identified in different forms of hereditary FSGS. Mutations of NPHS2 were detected in 26-38% of familial autosomal recessive steroid-resistant NS (SRNS), 6-19% of sporadic cases of SRNS, and in few adult patients with FSGS. Large multicenter studies demonstrated that patients with two pathogenic NPHS2 mutations have a very low risk of recurring FSGS after renal transplantation, whereas patients with only one mutation presumably have a risk comparable to non-NPHS2 FSGS patients. The management of FSGS following renal transplantation remains controversial. Following the assumption of a putative permeability factor, several studies have suggested the efficacy of plasmapheresis in inducing remission, preferably in conjunction with high-dose cyclosporine A or cyclophosphamide. Prospective studies will be necessary to better evaluate different therapeutic approaches.