The dominant part of human infections is associated with biofilm formations. Biofilm represents structured communities of bacterial or fungal cells enclosed in self-produced polymeric matrixes adherent to supporting surfaces. Microbial DNA and the host cell DNA, after their release at the infection site, show the ability to promote biofilm formation. Between the different constituents of biofilm matrixes, extracellular DNA (eDNA) may be the only component indispensable for the initial attachment and early biofilm formation through an enhanced matrix structural integrity. The effect of DNA on bacterial/fungal attachment is non-specific, as indicated by the stimulatory effect of plasmid, chromosome, or eukaryotic DNA. DNase I impaired bacterial biofilm growth and the targeting eDNA were recently proposed to eliminate and/or prevent different microbial infections associated with biofilm formations.