The discipline of hypothermic medicine (Cryo) covers a wide diversity of application areas ranging from organ transplantation to biopreservation of cells and tissues to cryoablation. With established techniques Cryo is often viewed as an “old school” discipline yet modern Cryo is in the midst of another scientific and technology development growth phase. In this regard, today’s Cryo finds itself at the forefront of research in the areas of molecular biology and engineering. While covering a wide range of temperatures (∼4°C to −196°C, nominally) and exposure times (minutes to years), each Cryo application utilizes low temperature to depress or halt biological activity on a transient or permanent basis. While the ultimate outcome desired may vary significantly (preservation vs. ablation) the overall response of a biologic to low temperature exposure share a number of commonalities, as well as differences, at the molecular level. Recent studies have shown that the control and direction of these molecular responses significantly impacts final outcome. This presentation will provide an overview of our current understanding of the molecular stress response of cells to low temperature exposure (ranging from ∼4°C to −196°C), the interrelated role of the apoptotic and necrotic cell death continuum and how this impacts outcomes in a diverse range of clinical and research settings including preservation and ablation. Further, discussion will include studies focused on the targeted modulation of common and/or cell specific responses to cold and freezing temperatures as a potential path to tailoring outcomes, from improved cell function to enhanced cancer ablation. This line of investigation has provided a new direction and molecular-based foundation guiding new research, technology development and procedures. As the use of and the knowledge base surrounding Cryo continues to expand this new path will continue to provide for improvements in overall Cryo efficacy and outcome.Disclosure: Author was or is employed by CPSI Biotech.