In aging populations, many patients have multiple diseases characterized by acceleration of the aging process including cardiovascular diseases, metabolic diseases, and chronic kidney disease. Remarkable progress in minimally invasive, interventional therapies, such as percutaneous coronary intervention and transcatheter aortic valve replacement has enabled patients who were previously not transplant candidates because of co-existing problems to become potentially viable candidates for lung transplantation. Recently, we have observed an outstanding and steady increase in patients older 70 years of age with multiple comorbidities who are referred to our high-volume center as potential candidates for lung transplantation. However, the impact of diseases characterized by an accelerated aging process and their treatments on transplant outcomes remains unclear. This review aims to highlight these challenges in the current era of lung transplantation, review the prior literature, and discuss future directions with a multidisciplinary view including translational research, transplant medicine, and surgery, as well as from a programmatic and administrative standpoint. © 2019 Steunstichting ESOT.