Plasma polymer films (PPFs) are well-known for their enhanced stability compared to conventional polymer coatings. However, PPFs tend to undergo aging in air or in aqueous environments due to oxidation, hydrophobic recovery, hydrolysis and dissolution of oligomeric fragments. Such aging mechanisms cause modifications of the PPFs that entail a change in surface properties. For example, PPF surfaces which are probed for protein adsorption or cell adhesion might therefore be substantially different from the initial PPF. It becomes thus necessary to understand the chemical reactions involved in the chemical modification (and/or degradation) of PPFs. Here, a summary of the most important aging mechanisms occurring in PPFs is given. More precisely, chemical reactions that can potentially occur in oxygen- and nitrogen-containing plasma polymer films when stored in air and in water were highlighted. On the basis of this understanding, recent strategies to reduce or delay aging mechanisms and/or to provide time-controlled degradable PPFs are discussed: the enhancement of the degree of cross-linking, the formation of a gradient structure in the PPF during plasma deposition, and the chemical post-plasma treatment to reduce the number of reactive sites. Finally, potential applications of such coatings will be considered.