Orthopedic surgery of total hip and total knee arthroplasty were the most successful orthopedic surgeries of the last century. In the context of an increase number of primary and revision total hip and total knee arthroplasty performed each year, an increased risk of complication is expected. The aim of our review is to present comprehensive data form the literature regarding the diagnosis strategies (according to the international guideline for the diagnosis of biofilm infections) and treatment strategies (irrigation and debridement with retention of components, one-stage or two-stage revision) for prosthetic joint infection. A MEDLINE via PubMed, Scopus, and Web of Science search for original and review articles was performed using key terms, prosthetic joint infection, PJI, biofilm, total hip arthroplasty, total knee arthroplasty, diagnosis, and treatment. Prosthetic joint infection, still, remains the most common and feared arthroplasty complication. Recent studies have shown that the formation of biofilm by pathogens is involved in prosthetic joint infection, infections that are acquired either via an exogenous or an endogenous pathway. The diagnosis and treatment of prosthetic joint infection remains a challenge. A correct diagnosis of infection is decisive for a correct treatment of orthopedic implantrelated infections.