For many years, the only specific pharmacologic intervention to decrease end-stage renal disease (ESRD) in diabetic kidney disease (DKD) was renin-angiotensin system (RAS) blockade. Recently, sodium-glucose co-transporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid antagonists (MRAs), and glucagon-like peptide-1 (GLP-1) receptor agonists have been introduced. However, there remains a need for new therapies. The non-specific phosphodiesterase inhibitor pentoxifylline (PTX) has been shown to have anti-proteinuric and anti-inflammatory effects, and small randomized clinical trials and meta-analyses indicate that PTX may have therapeutic benefits in DKD.