Failure of therapy for microbial infections may be related to a number of factors, a major one being drug resistance. Although much progress has been made during the past decade, agents are still needed for improved treatment of infections in which clinical success rates remain unsatisfactory. Problem pathogens include enteric bacteria such as Serratia species, Enterobacter species, and a number of nonfermenting gram-negative bacilli, including Pseudomonas species. Gram-positive organisms that continue to pose a significant therapeutic problem are the coagulase-positive and coagulase-negative staphylococci and enterococci. Atypical mycobacterial species offer major therapeutic challenges. No important broad-spectrum antifungal agents of low toxicity have been developed during the past two decades. Any new antibacterial or antifungal agent should be potent, safe, and well tolerated and should possess pharmacokinetic advantages that will lead to more simplified dosing; low cost would be an additional important advantage.