Ceftriaxone is a third-generation of cephalosporins which is used for community acquired infections such as pneumonia and urinaly tract infections. It showed great advantage of once-daily administration based on pharmacological manner and need no renal impairment. It is stable for β-lactamases against first-or second-generations of cephalosporins. Ceftriaxone is also used for streptococcal endocarditis as alternative first-line therapeutic regimen and used for Sexually Transmited Disease (STD) such as syphilis and chancoroid. Due to its pharmacological advantage, Ceftriaxone is used for Outpatient Parenteral Antibiotic Therapy (OPAT) with sufficient clinical efficacy in the world. This review focused on therapeutic option or alternative first line therapy of Ceftriaxone and Ceftriaxone in OPAT. The reappraisal of 'traditional antibiotics', such as ceftriaxone, has triggered a review of adequate antibiotic treatment.