An important strategy to circumvent the problem of antimicrobial resistance is to search for new compounds with antimicrobial activity. In this context, aminosterols, which include squalamine-like compounds and ceragenins, have gained interest due to their wide spectrum of antibacterial and antifungal properties. In light of recently reported data, we decided to analyze the mechanism of action of these compounds as well as their antimicrobial properties. Aminosterols are active against both bacterial reference strains and multidrug-resistant antibiotics as they disrupt the integrity of the bacterial membrane. Thus, these compounds could be useful in the development of new topical decontaminants or disinfecting agents.