Although several antibiotics are already widely used against a large number of pathogens, the discovery of new antimicrobial compounds with new mechanisms of action is critical today in order to overcome the spreading of antimicrobial resistance among pathogen bacteria. In this regard, marine organisms represent a potential source of a wide diversity of unique secondary metabolites produced as an adaptation strategy to survive in competitive and hostile environments. Among the multidrug-resistant Gram-negative bacteria, Pseudomonas aeruginosa is undoubtedly one of the most important species due to its high intrinsic resistance to different classes of antibiotics on the market and its ability to cause serious therapeutic problems. In the present review, we first discuss the general mechanisms involved in the antibiotic resistance of P. aeruginosa. Subsequently, we list the marine molecules identified up until now showing activity against P. aeruginosa, dividing them according to whether they act as antimicrobial or anti-virulence compounds.