The recent emergence of resistance towards antimicrobial agents, especially towards antibiotics, among bacteria demands innovation and improvements in the current strategies employed to fight bacterial infections. To understand the processes that are involved in infection and the potential development of resistance requires a clear understanding of antimicrobial interfaces, where the antimicrobial agent interacts with its target. This chapter will focus on our current understanding of antimicrobial interfaces which may serve as the starting point in antimicrobial resistance. The chapter will first discuss the initial physicochemical process involved in bacterial attachment, cell–cell communication, biofilm formation and its dispersion. The role of biofilms in infection is discussed further along with the biofilm antimicrobial surface interface. This is followed by biomaterial design challenges which include anti-adhesive surfaces, contact active materials followed by controlled drug delivery agents. Towards the end of the chapter the role of veterinary antibiotic use in human antimicrobial resistance and its control strategies are also discussed.