Antibiotic-loaded bone cement has been in use for over 30 years for the fixation of total joint arthroplasties, although its mechanism of action is still poorly understood. This review presents the backgrounds of bone cements, prosthesis-related infection and antibiotic-loaded bone cements. It is shown that antibiotic-loaded bone cement has a significant effect on bacteria, particularly in animal and clinical studies. However, recently, antimicrobial resistance among bacteria has been ascribed to the antibiotic-loaded bone cement. The unresolved issues both regarding the action of antibiotic-loaded bone cement and the nature of the antimicrobial resistance necessitate further research into the interaction of antibiotic-loaded bone cement and bacteria.