Many microbes are able to interfere with solid surfaces and trigger highly sophisticated colonization responses that include expression of specific properties such as increased resistances to antimicrobial agents. An anticontamination strategy might be to prevent adhesion by interfering with the surface-sensing processes and repelling the pioneering cells, to maintain the cellular sensitivity to antimicrobial agents. Recent studies have shown that differences in the physiological state of free-floating and attached bacteria, which could explain the increased levels of resistance, are triggered very early during attachment. Two-component-mediated signalling mechanisms are involved in these surface-sensing processes. Drugs and surface treatments able to interfere with the stimulation factors of these sensing systems (water activity and accumulation of proteins within the periplasm) could "blind" the colonizing bacteria and delay surface contamination.