We read with great interest the recently announced 2024 European Society of Cardiology (ESC) guidelines on the management of chronic coronary syndromes (CCS), which provide important guidance for clinical practice [ ]. A well-known pitfall of percutaneous coronary interventions is in-stent restenosis (ISR), which occurs in 10 % of patients at 10 years follow-up [ ]. The optimal management method for this significant clinical problem is, though, still unanswered, with available options being either reimplantation of a drug-eluting stent (DES) or balloon angioplasty with drug-coated balloons (DCB). Per 2024 ESC guidelines, there is an IA recommendation for implanting a drug eluting stent in patients with in-stent restenosis, which should be, thus, preferred from a DCB. Given the expansion of use of DCBs and the implications of re-stenting an in-stent restenosis area, there are several gaps in knowledge in order to fully support this recommendation.