Biofilms are complex, surface-attached microbial communities embedded within a self-produced extracellular polymeric substance (EPS). They pose a significant challenge in healthcare settings, especially in association with indwelling medical devices such as catheters, prosthetic joints, and cardiovascular implants. These infections are often persistent, resistant to antimicrobial treatment, and difficult to eradicate, leading to prolonged hospital stays, increased healthcare costs, and morbidity. The formation of biofilms on medical devices has been well documented since the seminal work of Costerton and colleagues in the late 20th century, highlighting the transition from planktonic to sessile growth as a key virulence factor (Costerton et al., 1987).Biofilm formation follows a multi-step process involving initial bacterial attachment, microcolony formation, maturation into a three-dimensional structure, and eventual dispersion. This process is regulated by environmental cues and microbial gene expression, including quorum sensing, a communication system that coordinates group behavior (Fuqua et al., 1994). Common biofilm-forming organisms in clinical settings include Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans. These pathogens exhibit altered phenotypic states within biofilms, contributing to antimicrobial resistance and immune evasion (Donlan & Costerton, 2002).Genomic studies have provided insights into the molecular mechanisms underpinning biofilm development and persistence. Early transcriptomic analyses and gene knockout studies have identified key genes involved in EPS synthesis, surface adhesion, and resistance mechanisms (Whiteley et al., 2001). The role of mobile genetic elements and horizontal gene transfer in enhancing biofilm-associated resistance is also noteworthy. These findings underscore the need for genomic approaches to better understand biofilm heterogeneity and to identify potential therapeutic targets.One of the major concerns with device-associated biofilm infections is their chronic nature and tendency to recur after conventional treatment. Traditional antimicrobial therapies often fail due to the limited penetration of drugs into the biofilm matrix and the presence of dormant, metabolically inactive cells known as persisters. Consequently, genomic-based strategies, including antisense RNA, phage therapy, and CRISPR-Cas systems, are being explored as alternatives to conventional treatment (Mah & O'Toole, 2001).This review aims to synthesize historical and foundational perspectives on biofilm formation with recent genomic insights to provide a comprehensive understanding of biofilm-associated infections in medical devices. By integrating early discoveries with contemporary genomic data, this article highlights the ongoing need for multi-disciplinary approaches to combat biofilm-mediated infections. Moreover, the review discusses the implications for clinical practice, including the need for biofilm-resistant materials and improved diagnostic methodologies.