Functionalized poly(p-xylylenes) constitute a versatile class of reactive polymers that can be prepared in a solventless process via chemical vapor deposition (CVD) polymerization. The resulting ultrathin coatings are typically pinhole-free and can be conformally deposited onto a wide range of substrates and materials. More importantly, appropriately selected functional groups can serve as anchoring sites for tailoring biointerface properties via the immobilization of biomolecules. In this article, controlled surface chemistries are outlined that use functionalized poly(p-xylylenes) as reactive coatings, including alkyne-functionalized coatings for Huisgen 1,3-dipolar cycloaddition reactions or aldehyde-functionalized coatings. The reactive coatings technology provides flexible access to a range of different surface chemistries, enabling a broad range of potential applications in microfluidics, medical device coatings, and biotechnology. In this feature article, we will highlight recent progress in vapor-based reactive coatings and will discuss potential benefits and current limitations.