Since the discovery of carbenicillin in 1970, several groups of beta-lactam agents with remarkable activity against P. aeruginosa are actually available among penicillins such as ticarcillin, azlocillin, piperacillin, apalcillin and among cephalosporins: cefoperazone, cefsulodin as well as new structures including monobactams (aztreonam) and carbapenems with imipenem. An attempt to establish hierarchy in terms of weight for weight activity, particularly against susceptible isolates is made. The most active antimicrobial agents are: imipenem, apalcillin, ceftazidime, cefsulodin, piperacillin and azlocillin. The bactericidal activity is reported for virtually all of them but more accurate techniques such as time-killing curves are needed to make comparisons, because some discrepancies were reported. Nevertheless, among several factors affecting their inhibitory and bactericidal activities, some of them appeared predominant: inoculum effect and beta-lactamases. The different behavior of beta-lactam antibiotics may be in relation with other mechanisms such as impermeability. A few surveys on the resistance mechanism indicated that impermeability can be prevalent, instead beta-lactamases. But in any case, the enzyme distribution showed carbenicillinases (PSE-1, PSE-4) and OXA were observed with a high prevalence among ticarcillin-resistant isolates and more recently cephalosporinases. These drugs acted synergistically with all of the aminoglycosides in vitro against P. aeruginosa isolates and also in animal models of infection. If the synergism appeared to play a major role in the therapy of P. aeruginosa infections, these new beta-lactam antibiotics offer the possibility of other approaches to combination therapy.