 Biofilms are complex communities of microorganisms that form on living or non-living surfaces. They can cause persistent infections, increased antibiotic resistance, and recurrent infections. Current and emerging anti-biofilm strategies focus on disrupting quorum sensing, preventing bacteria from attaching to surfaces, interfering with bacterial aggregation in mucus layers, degrading the extracellular polymeric matrix, and using nanoparticles to target persistent cells within the biofilm core. However, these strategies face challenges such as limited effectiveness in vivo, potential cytotoxicity to host cells, and the propensity to illicit resistance in targeted biofilm-forming microbes. Next-generation anti-biofilm strategies, which combine multiple approaches, have been developed and are being advanced through recent advancements in nanotechnology, synthetic biology, and antimicrobial drug discovery. Assessments of current anti-biofilm mitigation approaches, as presented here, can help guide future initiatives towards innovative anti-biofilm therapeutic strategies. This article was authored by Ahmed G. Abdulhamid and Ahmed E. Yousef. We are article.tv, links in the description below.