Functionalized poly- p -xylylenes establish a unique class of reactive polymers that are useful for biomimetic and spatially directed surface engineering. Reactive coating technology uses chemical vapor deposition (CVD) polymerization to deposit a wide range of chemical signatures on various substrate materials. Its simplicity in providing chemically reactive groups and its applicability to three-dimensional geometries (e.g., for microfluidics) enables exact tailoring of surface properties and the preparation of biologically relevant microenvironments. Reactive coatings are compatible with soft lithographic processes allowing for patterning of proteins, DNA, cytokines, and mammalian cells. Current trends regarding polymer-based surface engineering approaches, and more specifically, functionalized poly- p -xylylenes, are discussed.