Antipseudomonal penicillins retain most of the antibacterial activity of penicillin and aminopenicillins. This group of penicillins has added activities against many gram-negative rods, including P. aeruginosa. Similar to the earlier penicillins, this group continues to be susceptible to hydrolysis by many beta-lactamases and are, therefore, not consistently active against Staphylococcus, some gram-negative rods, and certain beta-lactamase-producing gram-negative anaerobes. The ureidopenicillins, especially piperacillin, appear to have better activity against Enterococcus, Klebsiella, and P. aeruginosa than ticarcillin. The advantages over the newer cephalosporins are (1) better activity against Enterococcus, (2) more consistent activity against Clostridium, and (3) more consistent synergy with aminoglycosides. The ureidopenicillins have certain advantages over carboxypenicillins, including lower sodium load, less frequent hypokalemia, reduced platelet dysfunction, minimal dosage adjustment in patients with renal failure, and a wider spectrum of antibacterial activity, especially against Enterococcus, Pseudomonas, and Klebsiella. The utility of the antipseudomonal penicillins by themselves is limited as agents for monotherapy when the infecting organism is not known. In addition, monotherapy is not recommended in certain infections to avoid the development of resistance. When combined with a beta-lactamase inhibitor or with an aminoglycoside, however, some of the weaknesses can be overcome.