Synthetic peptides based on naturally occurring antimicrobial peptides (AMPs) represent promising antibacterial agents. Now, de Breij and colleagues have synthesized novel peptides with improved antimicrobial and antibiofilm activities (SAAPs), based on a principle human AMP, LL-37. The most potent of these, SAAP-148, was effective against a panel of multidrug- resistant pathogens, including an Escherichia coli isolate resistant to colistin. SAAP-148 prevented biofilm formation by Staphylococcus aureus and Acinetobacter baumannii, and eliminated established biofilms and persister cells. SAAP-148 ointment completely eradicated acute and established methicillin-resistant S. aureus and A. baumannii infection from mouse skin in vivo and wounded human skin ex vivo.