Synthetic polymers are attracting great attention in the last decades for their use in the biomedical field as nanovectors for controlled drug delivery, hydrogels and scaffolds enabling cell growth. Among them, polymers able to respond to environmental stimuli have been recently under growing consideration to impart a "smart" behavior to the final product, which is highly desirable to provide it with a specific dynamic and an advanced function. In particular, thermo-responsive polymers, materials able to undergo a discontinuous phase transition or morphological change in response to a temperature variation, are among the most studied. The development of the so-called controlled radical polymerization techniques has paved the way to a high degree of engineering for the polymer architecture and properties, which in turn brought to a plethora of sophisticated behaviors for these polymers by simply switching the external temperature. These can be exploited in many different fields, from separation to advanced optics and biosensors. The aim of this review is to critically discuss the latest advances in the development of thermo-responsive materials for biomedical applications, including a highly controlled drug delivery, mediation of cell growth and bioseparation. The focus is on the structural and design aspects that are required to exploit such materials for cutting-edge applications in the biomedical field.