Therapy for endocarditis due to Pseudomonas aeruginosa is complicated by the emergence of resistance during therapy, lack of universally available synergistic antimicrobial agents, and unacceptably high morbidity and mortality rates. The authors report a case of aortic valve endocarditis due to P. aeruginosa in which resistance to piperacillin developed during combined therapy with tobramycin. Bacteriologic cure was obtained with a combination of imipenem/cilastatin and tobramycin. The authors review six other cases of P. aeruginosa endovascular infections treated with imipenem.