Ceftriaxone possesses a broad spectrum of antimicrobial activity that includes the Gram-positive and Gram-negative aerobes commonly associated with serious infections. Its therapeutic efficacy is comparable to that of other third-generation cephalosporins and aminoglycoside-combination regimens. The most commonly reported adverse events with ceftriaxone are similar in incidence and severity to those reported with other third-generation cephalosporins. Notably, the drug has a favourable pharmacokinetic profile which allows once-daily administration. In comparative studies with other parenteral regimens requiring 3 to 6 daily doses, treatment with once-daily ceftriaxone reduced total antimicrobial drug costs (i.e. acquisition, preparation and administration costs) by 17 to 52%. Ceftriaxone was also more cost effective than ceftazidime and a variety of other antimicrobial treatment regimens (penicillins, cephalosporins, combination regimens) in the treatment of patients with community-acquired pneumonia or bronchopneumonia. This reflected lower drug and hospitalisation costs associated with a reduced length of hospital stay in ceftriaxone recipients. In noncomparative studies, ceftriaxone achieved considerable hospitalisation cost savings in patients with serious infections (mostly bone, joint, skin/skin structure infections), who were able to receive all or part of their antimicrobial therapy as outpatients. In one analysis which evaluated all direct and indirect costs (such as training programmes, transportation, time for visits and supplies) and benefits (such as hospitalisation cost savings, return to work or school, increased productivity) of outpatient ceftriaxone therapy, the overall benefit-cost ratio was approximately 5 : 1. The studies to date confirm that ceftriaxone is effective, well tolerated, convenient to administer and, when utilised appropriately, offers the potential for cost avoidance in patients with serious infections. Although additional well designed pharmacoeconomic analyses are needed to further evaluate its cost effectiveness, ceftriaxone should be considered an essential third-generation cephalosporin formulary representative in most clinical settings.