The interventional treatment of coronary artery disease (CAD) has undergone significant improvements thanks to technological innovations. Nowadays, percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is the standard of care for the treatment of CAD. Nevertheless, the non-negligible incidence of in-stent restenosis (ISR) and suboptimal results in various anatomical settings has led to the development of drug-coated balloons (DCBs). DCBs are catheter-based balloons whose surface is coated with an anti-proliferative drug (mainly Paclitaxel or Sirolimus) loaded onto the balloon surface with different technologies and dose concentrations. In the beginning, these devices were used for the treatment of ISR showing an excellent efficacy profile in the inhibition of intimal hyperplasia. Subsequently, several studies evaluated their use in other angiographical and clinical contexts such as de novo lesions, small vessel disease, diffuse coronary disease, bifurcation lesions, acute coronary syndromes, high-bleeding risk and diabetic patients. This comprehensive review aims to describe the main DCB platforms on the market, their fields of application with the main supporting studies and their future perspectives.