Polyurethanes (PURs) are versatile polymers used in a wide variety of fields, such as the medical, automotive, textile, thermal insulation, and coating industries as well as many everyday objects. Many PURs have applications that require a long service life, sometimes with exposure to aggressive conditions. They can undergo different types of physicochemical and biological degradation, but they are not compostable, and many of them constitute persistent waste in the environment. Although both bacteria and fungi can be involved in the degradation of PURs, fungi are often the main biodegradation agents. The chemical structure of PURs determines their degree of biodegradation. Fungal biodegradation of PURs is linked to the production of enzymes, mainly esterases and proteases, alongside laccases, peroxidases, and tyrosinases, which can modify the structure of polyurethane compounds by forming carbonyl groups. The experimental analysis of the biodegradation of PUR can be carried out by bringing the polymer into contact with a mold in pure culture or with a microbial consortium. Then, global measurements can be taken, such as weight loss, tensile tests, or the ability of microorganisms to grow in the presence of PUR as the sole carbon source. The analysis of the chemical structure of the polymer and its degradation products after fungal growth can confirm biodegradation and specify the mechanism. The main avenues of future research are directed towards the development of fully biodegradable PURs and, on the contrary, towards the development of PURs that are more resistant to degradation phenomena, in particular biodegradation, for applications where the material is in contact with living organisms.