The community established by the association of microorganisms such as bacteria, yeast, or fungi leads to biofilm formation. Microorganisms are embedded in the extracellular polymeric matrix of biofilm adhering to biotic and abiotic surfaces or substratum. Biofilm can grow on medical devices, living tissues, or implants and cause infection in patients. Biofilm is a resistant microbial community due to the expression of the gene that causes its resistance to antibacterial agents and human immunity. These microbial infections are prone to occur in healthcare facilities and are the major sources of morbidity and mortality among patients. Cardiac implants based on cardiac implantable electronic devices-related infections account for 30% of death due to infection associated with Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli, Acinetobacter baumannii, Staphylococcus epidermidis, and Propionibacterium acnes. This chapter includes the role of nanoparticles in the prevention of biofilm on medical devices and human implants. Nanoparticles have important physicochemical properties that inhibit the proliferation of infectious microorganisms and prevent biofilm formation. Nanoparticles follow diverse mechanisms for antibiofilm activities leading to oxidative damage and genetic changes in microorganisms. Nanoparticles could be superior alternatives to conventional antibiotics. Various types of nanomaterials based on lipids, polymers, and metals show excellent potential toward antimicrobial growth. Nanomaterial coverings or coatings on medical devices, healthcare kits, and implants can overcome the biofilm associated with infection and mortality. © 2019 American Chemical Society. All rights reserved.