Idiopathic focal segmental glomerulosclerosis is a histologic diagnosis that usually presents as the nephrotic syndrome but, unlike minimal change disease, often leads to renal failure in children. Standard therapies used to treat the proteinuria are often futile, and thus patients are at risk for the multiple complications resulting from persistent, severe proteinuria. Eventually, end-stage renal failure ensues, and the possibility of the disease recurring in the transplanted renal allograft is worrisome. This report reviews the clinical features and outcomes of idiopathic focal segmental glomerulosclerosis in children, the response to newer treatment options, and new insights into understanding what factors may be involved in causing the disorder.