Multiple drug-resistant bacterial strains are showing new different mechanisms to overcome the antimicrobial action which reduces the efficacy of conventional antibiotics [1]. Therefore, drug discovery research has focused on developing fast, effective and safe alternatives to prevent this multiresistance. Phlorotannins are a diverse class of polyphenols, secondary metabolites described in brown algae, that are mainly constituted of polymers of phloroglucinol and depending on their linkage and structure can be classified mainly as fucols, fucophlorethols, eckols and phloroethols [2]. These polyphenols have been described in both macro- and microalgae, suggesting that they can be recovered from a great variety of sources [2]. Phlorotannins have been extensively described to possess several biological properties, foremost as antioxidant and antimicrobial compounds. Several in vitro reports have described that phlorotannins showed growth inhibition and bactericidal effects against Gram + (e.g. Bacillus cereus, Streptococcus pneumoniae, Staphylococcus aureus) and Gram ‒ bacteria (e.g. Salmonella sp., Campylobacter jejuni, Pseudomonas aeruginosa), also including antibiotic-resistant strains like MRSA [3]. Although the mechanisms of action of this group of compounds has not been fully elucidated, tannins are described to interact with membrane proteins and key metabolic enzymes, impeding bacterial growth and resulting in membrane lysis [3,4]. Moreover, different phlorotannins were able to inhibit bacterial biofilm formation, production of quorum-sensing molecules, and also viral replication (e.g. influenza) [5,6]. Few in vivo studies support their effectiveness as antibiotics, whereas clinical trials studying other properties, consistently report high bioavailability and null toxicity of phlorotannins [6,7]. Considering current evidence, phlorotannins could be considered as interesting candidates for antibiotic therapy clinical trials. The diversity of these natural compounds provides a promising gateway for researchers and the pharmaceutical industry to develop novel nontoxic, cost-effective and highly efficient antibacterial formulations with a broad scope of applications. This review focuses on potential use of phlorotannins as natural antimicrobial compounds, supported by scientific evidence.