Biofilms formed by multidrug resistant (MDR) bacteria like methicillin-resistant Staphylococcus aureus (MRSA) and others are the main causes of infections that represent a serious public health issue. Persistent MDR infections are mostly derived from biofilm formation which in turn leads to resistance to conventional antimicrobial therapy. Inhibition of bacterial surface attachment is the new alternative strategy without affecting the bacterial growth. Thus, the discovery of compounds that interfere with biofilm production, virulence factors release and quorum sensing (QS) detection in pathogens is a promising processus. Among these compounds, natural and synthetic molecules are a compelling alternative to attenuate pathogenicity. The combination of these compounds with antibiotics makes the bacteria more vulnerable to the later, once used alone. This combination can restore antibiotic effectiveness against MDR bacteria. Among these molecules, 3-phenylpropan-1-amine (3-PPA) has been found to inhibit Serratia marcescens biofilm formation, PAβN has been proven to inhibit biofilm prodcution in A. baumannii, while brominated Furanone C-30 has been reported to be a potent inhibitor of the QS system and P. aeruginosa biofilm. Therefore, the combination between biofilm-inhibitors and antibiotics represents a promising strategy to mitigate antibiotic resistance in MDR pathogens, which has become a major threat to public healthcare around the globe.