ABSTRACT Reactive chemical vapor deposition (CVD) polymerization provides a substrate‐independent platform for effective functionalization of virtually any solid substrates, flat, or curved, even with complex geometries. This article reviews bioactive surface functionalization strategies based on CVD polymerization and highlights commonly used surface chemistries. These reactions include alkyne–azide “click” chemistry, reactions of active esters with amine, aldehydes/ketones with hydrazides and alkoxyamines, thiols with alkenes and alkynes and surface‐initiated atom transfer radical polymerization. The resulting biofunctional surface coatings can facilitate orthogonal immobilization of more than one type of ligand on a substrate. CVD polymer coatings with nanoscale thicknesses are widely applicable in biomedical applications and can be easily integrated into micro‐ and nanodevice fabrication. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40315.