On a fundamental level, plasma is generated when a powerful energy source is used to excite matter (e.g., gas or vapour) to a stage beyond that of gases, where the molecules constituting the original matter are fragmented and a cocktail of chemically and biologically reactive charged and unstable particles is produced. These species then react with any surface they come in contact with, be it that of a liquid, solid substrate, or membrane proteins of the living organism, the reactions promoted by catalytic activity of plasma-generated electromagnetic radiation and heat. In the area of biofilm control, these reactions can be harnessed to engineer surfaces that prevent the initial stages of biofilm formation, or to create environmental perturbations and induce metabolic, genetic and epigenetic modulations sufficient to kill bacteria that manage to attach to these surfaces. This work considers several important aspects of plasma treatment that thus far may not have received due attention -the effect of physical environment, i.e., surface topography and electrical properties of the substrate on the quality of biofilm-retarding costings, and on inactivation efficacy, biofilm removal, and recolonization potential in the case of direct plasma treatment. This work demonstrates that the properties of bioactive polymer coatings assembled from terpinene-4-ol and tea tree oil on the surface of substrata with different surface morphology under low-pressure plasma conditions differ, in some instances substantially. This difference in bioactivity arises from the non-uniform assembly of the polymer on the surfaces with features of certain dimension and distribution under plasma conditions due to the non-uniform delivery of building and etching species from the gas phase to the surface. This research also demonstrates that atmospheric pressure plasma treatment used to remove biofilms from surfaces inadvertently changes the properties of the substrata, with the nature and extent of these changes being dependent on the chemical and morphological properties of the substrata. Here, the chemistry of the surface appears to play a critical role. The significance of these changes in defining cell-surface interactions is dependent on the type of substrata, e.g., biocide eluting versus contact killing, as well as on the properties of cells and cell culture conditions. For certain combinations of material and plasma-treated media, the antimicrobial activity of the substrata is enhanced. This provides a possible path for the design of more effective systems of active materials and decontamination (maintenance) treatments based on plasmas. In addition, this work also demonstrated that in some cases, sub-lethal doses of plasma exposure on Pseudomonas aeruginosa and Staphylococcus aureus bacterial cells potentially enhances their ability to recolonise surfaces, and renders cells more resilient to subsequent plasma treatments. The response is different for cells from different species, as well as for cells grown as mixed cultures. This is an important consideration for real-life uses of plasma treatment on implants, where implant ageing through wear and corrosion, and associated pitting and cracking may provide cells with ‘safe heavens’ to evade lethal doses of plasma.