Ceftolozane is a cephalosporin similar to ceftazidime in its structure, which is marketed in combination with tazobactam, a well-known β-lactamase inhibitor. After a brief introduction on the drug characteristics and efficacy, we focused on available data from randomized controlled trials and post-marketing observational studies pertaining to the safety of ceftolozane/tazobactam (C/T) for the treatment of complicated urinary tract infections (cUTI). A search was conducted in PubMed from January 2010 to February 2023. The use of C/T for the treatment of cUTI is supported by solid efficacy and safety data, especially for the treatment of those pathogens where it can represent a first-line approach due to some peculiar characteristics: (i) treatment of cUTI caused by multidrug-resistant Pseudomonas aeruginosa, in view of its frequent activity against carbapenem-resistant isolates when resistance mechanisms other than production of carbapenemases are concerned; (ii) treatment of cUTI caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales in those settings where the selective pressure for carbapenem resistance needs to be relieved, as a suitable and effective carbapenem-sparing option. Although development of resistance to C/T during or after treatment has been reported, this has been reported very rarely in patients receiving C/T for the treatment of cUTI.