Objective: To study changes in the susceptibility of Serratia spp. in Crete, Greece (2010–2015).Methods: Non-duplicate isolates were examined using automated systems. Phenotypic confirmatory tests were applied.Results: Three hundred and seventy-eight Serratia spp. were analyzed. Serratia marcescens (88.3%) was the predominant species. Fluoroquinolones (97.9%), carbapenems (97.4%) and fosfomycin (97.4%) were the most active followed by amikacin (95.5%), piperacillin/tazobactam (94.7%), and trimethoprim/sulfamethoxazole (94.4%). The activity of 3rd and 4th generation cephalosporins was 87–88.6%. The distribution of multi-drug resistant (MDR) strains varied, with a trend towards increasing frequency. ESBL (7.9%), carbapenemase (2.9%), AmpC (2.1%) and aminoglycoside modifying enzyme (10.6%) production were the commonest resistant phenotypes.Conclusion: The susceptibility of Serratia spp. varied during the study period a trend towards decreasing susceptibility, especially for non-carbapenem β-lactams and aminoglycosides.