Biofilms are communities of microbes encased within a self-produced matrix of exopolysaccharides. Microbes tend to prefer this lifestyle over the planktonic state because biofilms offer protection from environmental stresses, including antimicrobial agents. Cells within biofilms exhibit significantly greater resistance to antibiotics compared to their planktonic counterparts. Several factors contribute to this enhanced antibiotic resistance, including limited penetration of antibiotics, specific microenvironmental conditions within the biofilms, the presence of a subpopulation known as persister cells, and quorum-sensing mechanisms. This chapter explores the antibiotic resistome, which refers to the collection of antibiotic-resistant genes present in biofilms. It distinctly describes the antibiotic resistome of biofilms from various sources, including medical infections, drinking water distribution systems, wastewater treatment plants, and natural environments like rivers and estuaries, as well as biofilms found on plastic surfaces. Additionally, it discusses certain antibiotic-resistant genes (ARGs) that provide biofilm-specific resistance against antibiotics. The chapter also includes a discussion on horizontal gene transfer (HGT) in relation to biofilms.