Combined heart-liver transplantation (CHLT) is increasingly prevalent due to surgical and immunosuppression advancements. Indications for CHLT include familial amyloidosis, cardiac cirrhosis, dilated cardiomyopathy, and homozygous familial hypercholesterolemia. Challenges include hemodynamic instability and prolonged cold ischemia. Ex situ normothermic machine perfusion (NMP) offers a paradigm shift, allowing extended preservation times, facilitating hemodynamic stabilization post-cardiac surgery, and reducing metabolic disturbances during hepatic reperfusion. This article describes the first three CHLT procedures using ex situ NMP at Mayo Clinic Florida, highlighting its potential benefits.