 Abstract immunotherapy using chimeric antigen receptor, CAR, engineered T-cells has shown promising results in treating certain types of cancer. However, it has not yet been successfully applied to treat non-blood-related cancers such as those found in the solid organs. This review discusses some of the challenges associated with applying CAR T-therapies to solid tumours, including target selection, trafficking of engineered cells to tumour deposits, overcoming physical, chemical, and biological barriers to immune effector function, and selecting the most appropriate host cells for CAR engineering. Several pre-clinical technologies have been developed to address these challenges, and recent advancements in cellular engineering and manufacturing should lead to more effective treatments in the near future. This article was authored by John Mayer.