Perfluorocarbons (PFCs) are organic liquids derived from hydrocarbons in which some of the hydrogen atoms have been replaced by fluorine atoms. They are chemically and biologically inert substances with a good safety profile. They are stable at room temperature, easy to store, and immiscible in water. Perfluorocarbons have been studied in biomedical research since 1960 for their unique properties as oxygen carriers. In particular, PFCs have been used for liquid ventilation in unusual environments such as deep-sea diving and simulations of zero gravity, and more recently for drug delivery and diagnostic imaging. Additionally, when delivered as emulsions, PFCs have been used as red blood cell substitutes. This narrative review will discuss the multifaceted utilization of PFCs in therapeutics, diagnostics, and research. We will specifically emphasize the potential role of PFCs as red blood cell substitutes, as airway mechanotransducers during artificial placenta procedures, as a means to improve donor organ perfusion during the ex vivo assessment, and as an adjunct in cancer therapies because of their ability to reduce local tissue hypoxia.