Recently, biofuels have become a strategic focus to reduce vehicle emissions and increase sustainability of the transport sector. However, the sustainability of biofuels production has been questioned owing to its implications for future land footprint. In this respect, the EU Commission has very recently classified as low indirect land-use change (ILUC)–risk biofuels those obtained by crops grown on marginal lands and with low external inputs. Only few crops can reach high yields under both of these conditions across Europe. From this point of view, Jerusalem artichoke (Helianthus tuberosus L.) is certainly a species worthy of remark since it has all the attributes to accomplish the aims of the updated EU Renewable Energy Directive (RED II). Starting from physiological aspects, the present review examines and summarizes literature on the ecology, genetic resources, agronomic practices and sustainability of this species. The goal is to point out the recent advances of research in Jerusalem artichoke (JA) potential as alternative biofuel feedstock and to identify what is still needed to better characterize its environmental benefits and agronomic performance.