The majority of patients with prosthetic joint replacement (arthroplasty) experience dramatic relief of pain and restoration of satisfactory joint function. In the United States, more than.5 million people have a primary arthroplasty each year. Less than 10% of prosthesis recipients have complications develop during their lifetime, commonly as a result of aseptic biomechanical failure, followed by prosthetic joint infection. The pathogenesis of prosthetic joint infection is related to bacteria in biofilms, in which they are protected from antimicrobial killing and host responses rendering these infections difficult to eradicate. Current microbiology laboratory methods for diagnosis of prosthetic joint infection depend on isolation of a pathogen by culture. However, these methods have neither ideal sensitivity nor ideal specificity. Therefore, culture-independent molecular methods have been used to improve the diagnosis of prosthetic joint infection. In the research setting, detection of 16S ribosomal deoxyribonucleic acid by polymerase chain reaction has been used in the molecular diagnosis of prosthetic joint infection. Various antibiofilm strategies directed at disruption of adherent bacteria are the focus of intense research to improve the detection of biofilm organisms and their eradication. In this article, molecular and antibiofilm approaches to prosthetic joint infection are reviewed.