Polyurethane (PU) elastomers represent an important class of segmented copolymers. Thanks to many available chemical compositions, a rather broad range of chemical, physical, and biocompatible properties of PU can be obtained. These polymers are often characterized by high tensile and tear strength, elongation, fatigue life, and wear resistance. However, their relatively high permeability towards gases and water as well as their biocompatibility still limits the PU's practical application, especially for biomedical use, for example, in implants and medical devices. In this review, the barrier and permeability properties of segmented PUs related to their chemical structure and physical and chemical properties have been discussed, including the latest developments and different approaches to improve the PU barrier properties.