Infection following placement of therapeutic implants is a devastating complication that results in pain, increased disability, and the need for aggressive therapeutic intervention. This implant-associated infection is very recalcitrant to treatment with antibiotics. Firstly, bacteria adhere to and secrete a biofilm on metallic surfaces, embedding the bacteria within a matrix that limits accessibility by antibiotics and/or immune surveillance. Secondly, eukaryotic cells can harbor viable bacteria, allowing establishment of latent infections. Current research efforts are centered around strategies to subvert the ability of microorganisms to colonize these implants, as well as to prevent their propagation in the space immediately surrounding the implant. Specifically, we have discovered that we can decorate the surfaces of metal implants with antibiotics and other anti-microbial agents to produce an implant that is resistant to colonization by bacteria. Currently, we are expanding the ability of the implant surface to be an active anti-infective agent while maximizing its biocompatibility. In parallel, we are investigating mechanisms of bacteria colonization of eukaryotic cells and how to harness the cells machinery to eliminate internalized bacteria. These studies span fields related to bioengineering, tissue engineering, biochemistry, and biology to produce new translational products that can improve the outcome of implantations.