This review discusses the molecular mechanisms that contribute to the ability of pathogenic bacteria in biofilm communities to resist antimicrobial therapy. Biofilms are surface-attached microbial communities encased in an extracellular matrix that are less susceptible to antimicrobial agents than planktonic cells. Biofilm-based infections are difficult to cure due to the high degree of recalcitrance in biofilm communities, which is caused by various mechanisms such as antimicrobial interaction with biofilm matrix components, reduced growth rates, and specific genetic determinants of antibiotic resistance and tolerance. These mechanisms work together to ensure the survival of biofilm cells even under aggressive antimicrobial treatment. The review summarizes historical and recent scientific data on biofilm resistance and tolerance mechanisms, and suggests future research directions. It highlights the differences between biofilm and planktonic cells, including physiological heterogeneity, distinct transcriptomes and proteomes, and the fact that biofilm cells are less susceptible to antimicrobial agents. The review also discusses the terms 'resistance' and 'tolerance', and the various methods used to measure biofilm susceptibility. It covers the major mechanisms of biofilm resistance and tolerance, including the biofilm matrix, antimicrobial penetration, polysaccharides, antibiotic-modifying enzymes, extracellular DNA, bacteriophages, and stress responses. The review emphasizes the importance of understanding these mechanisms to develop effective treatments for biofilm-based infections.This review discusses the molecular mechanisms that contribute to the ability of pathogenic bacteria in biofilm communities to resist antimicrobial therapy. Biofilms are surface-attached microbial communities encased in an extracellular matrix that are less susceptible to antimicrobial agents than planktonic cells. Biofilm-based infections are difficult to cure due to the high degree of recalcitrance in biofilm communities, which is caused by various mechanisms such as antimicrobial interaction with biofilm matrix components, reduced growth rates, and specific genetic determinants of antibiotic resistance and tolerance. These mechanisms work together to ensure the survival of biofilm cells even under aggressive antimicrobial treatment. The review summarizes historical and recent scientific data on biofilm resistance and tolerance mechanisms, and suggests future research directions. It highlights the differences between biofilm and planktonic cells, including physiological heterogeneity, distinct transcriptomes and proteomes, and the fact that biofilm cells are less susceptible to antimicrobial agents. The review also discusses the terms 'resistance' and 'tolerance', and the various methods used to measure biofilm susceptibility. It covers the major mechanisms of biofilm resistance and tolerance, including the biofilm matrix, antimicrobial penetration, polysaccharides, antibiotic-modifying enzymes, extracellular DNA, bacteriophages, and stress responses. The review emphasizes the importance of understanding these mechanisms to develop effective treatments for biofilm-based infections.