Biofilms play a central role in antimicrobial resistance and chronic infections, particularly in orthopedics, where they contribute to periprosthetic joint infections and fracture-related infections. This chapter outlines the stages of biofilm formation—adhesion, proliferation, maturation, and dispersion—and their mechanisms of resistance, including antibiotic penetration barriers, persister cells, efflux pumps, and immune evasion. Diagnostic challenges are addressed through advanced methods like sonication, PCR, and imaging techniques. Management strategies combine surgical debridement, systemic and local antibiotics, and, when needed, implant revision. Emerging therapies such as antimicrobial coatings, nanotechnology, enzymatic agents, and photodynamic treatments show promise in disrupting biofilms. Early detection and multimodal intervention are key to improving outcomes.