Cryosurgery is evolving from a focal therapy for cancer to one that can also treat cardiovascular and neural targets. For example, new focal therapeutic targets include the pulmonary vein (atrial fibrillation), arteries (renal denervation) and nerves (pain and plantar fasciitis). For cryosurgery to successfully compete with heat or other ablative technologies in these new targets, it will be necessary to carefully assess thermal response in these targets and adjacent tissues that can sustain collateral injury. Further, it will be necessary to understand the mechanism of action of each of the ablative technologies. This presents new challenges as the measurement and modeling of temperature in these thin anisotropic biological structures during thermal excursions is not well understood. Further, it begs the question of whether heat, cold, or other energy based technology is best suited to each of these targets to achieve localized destruction without collateral injury. In this talk, I will describe ongoing work in our lab and with our collaborators at UC Berkeley and Minnesota to measure thermal properties at mm and sub mm length scales. Further, I will highlight some preliminary data that hints at differences in mechanisms of action between cryo, heat and other energy based technologies that may lead to a better understanding and therefore application in each of these new targets.