Focal segmental glomerulosclerosis, which is a common glomerular disorder, manifests clinically with a nephrotic syndrome and has a high propensity for recurrence after kidney transplantation. The pathophysiology is currently unknown, and podocytes appear to be the target of one or several circulating factor(s) that lead to the recurrence of proteinuria after kidney transplantation. Identifying these circulating factor(s) and cells involved in its synthesis remains elusive; however, recently, our research on podocyte cytoskeleton biology has opened a new era of treatment. This review will highlight recent progress in the physiopathology of focal segmental glomerulosclerosis recurrence after transplantation and its treatment.