Local drug delivery of an anti-proliferative drug from balloon catheter systems to the site of arterial injury has been attempted repeatedly over the years with limited success in drug uptake and retention. Accessibility of the drug at the site is critical to combat the body's response to the procedural trauma of angioplasty. Recently, formulations have been designed which achieve delivery of therapeutic doses of the anti-proliferative drug paclitaxel to arteries with higher efficiency and longer tissue retention. These formulations succeed through formation of a drug reservoir in the artery wall enabling release after the initial angioplasty procedure. These formulations have become the cornerstone of several drug coated balloon (DCB) technologies which have found an initial, broad therapeutic application in the treatment of stenosis of the superficial femoral artery (SFA). DCBs achieve drug delivery while leaving no implant behind and represent a new class of combination products developed at the interface of engineering, chemistry and medical science. This review article summarizes the development of the LUTONIX® drug coated balloon catheter. The introduction of DCB technology has provided clinicians and patients with new SFA treatment options while ongoing clinical evidence in additional vascular beds is generated.