The damage and loss of podocytes is a primary hallmark of nephrotic syndrome. In the pursuit of targetable molecules that are involved in podocyte pathophysiology, some studies have identified B7-1 (also known as CD80) as a potential biomarker. Furthermore, B7-1 blockade has been proposed as a podocyte-specific treatment for patients with nephrotic syndrome who have limited therapeutic options, such as those with focal segmental glomerulosclerosis, minimal change disease, diabetic nephropathy and lupus nephritis. In this Perspectives article, we describe and compare supporting and contradicting data on the role of podocyte B7-1 in the pathogenesis of various podocytopathies. Moreover, we highlight crucial issues that should be addressed urgently - such as standardization of sample processing time, material conservation and antibody usage in immunohistochemical protocols - as a clinical trial that is investigating the efficacy of B7-1 blockade in treatment-resistant nephrotic syndrome is ongoing.