Bacteria that form biofilms are protected from antibiotic killing, contributing to the persistence of infections such as those associated with implanted devices. The protective mechanisms in biofilms differ from those responsible for conventional antibiotic resistance. These include poor antibiotic penetration, nutrient limitation, slow growth, adaptive stress responses, and the formation of persister cells. Each of these mechanisms may be a target for new chemotherapeutic agents, and disabling biofilm resistance could enhance the effectiveness of existing antibiotics against biofilm infections. The article reviews the genetic and molecular basis of these resistance mechanisms, highlighting the need for further research to understand and exploit these defenses.Bacteria that form biofilms are protected from antibiotic killing, contributing to the persistence of infections such as those associated with implanted devices. The protective mechanisms in biofilms differ from those responsible for conventional antibiotic resistance. These include poor antibiotic penetration, nutrient limitation, slow growth, adaptive stress responses, and the formation of persister cells. Each of these mechanisms may be a target for new chemotherapeutic agents, and disabling biofilm resistance could enhance the effectiveness of existing antibiotics against biofilm infections. The article reviews the genetic and molecular basis of these resistance mechanisms, highlighting the need for further research to understand and exploit these defenses.