Conventional therapies for transcatheter treatment of patients with infrainguinal obstructive disease remain compromised by high restenosis rates. Drug-coated balloons (DCB) offer a novel therapeutic alternative targeting the source of neo-intimal hyperplasia, without the need for a permanent endovascular scaffold and their inherent limitations. A systematic research of the medical databases (Pubmed) has been conducted for this up-to-date review. Key words, such as "drug-coated balloons" (DCB), "drug-eluting balloon," "in-stent-restenosis" (ISR), "de-novo stenosis," "plain old angioplasty," "atherectomy," "debulking," "superficial femoral artery," "popliteal artery," "above/below the knee," and "peripheral artery disease" have been used for literature search. Furthermore, data from reviews, original contributions, randomized controlled studies, observational studies, registries and single center experiences have been considered. Overall, an increasing level of evidence supports the use of DCB for the treatment of long, complex, heavily calcified femoropopliteal non-occlusive and occlusive lesions, including failure after BM stent implantation due to ISR. However, more studies will be necessary to investigate the long-term effects of DCB-treatment in these real-world lesions.