Over the last 50 years, biomaterials, prostheses and implants saved and prolonged the life of millions of humans around the globe. Today, nano-biotechnology, nanomaterials and surface modifications provides a new insight to the current problem of biomaterial complications, and even allows us to envisage strategies for the organ shortage. In this talk, creative strategies for modifying and engineering the surface and the interface of biomaterials, including metals, polymers from natural and synthetic sources, will be discussed. The unique potential of low-pressure low-temperature plasma surface modification will be detailed with the overall aim to envisage today how far innovation can bring tomorrow solutions for reparative and regenerative medicine. Applications for health will be emphasized, including biologically active-based, biomimetic, low-fouling, bactericidal, and antiviral coatings.