In response to the initiatives of orthopedic surgeons, the incidence of infection following total hip arthroplasty has decreased in medical centers specializing in hip surgery but remains greater than 1% in the United States. When infection does compromise total hip arthroplasty, there is no one test that can establish the diagnosis, especially when there is a differential diagnosis between aseptic and low-grade septic loosening. Newer techniques involving improved scintigraphic compounds, molecular tests, and immunologic examinations are in use. The microbiology of the infection is critical to the patient's response and the ability of the orthopedic surgeon to treat the infection and restore function to the extremity. In recent years the emergence of enzymatic resistance to microorganisms frequently has necessitated the administration of potentially toxic antimicrobial agents not used in the past. European physicians have initiated novel treatments of patients with an infected total hip arthroplasty with a combination of oral agents such as fluoroquinolone and rifampin over a period of 6 months without concomitant surgical intervention; preliminary reports on this treatment are encouraging.