The diagnosis of infections in patients with arthritis and/or joint prostheses requires interdisciplinary cooperation and the use of up-to-date methods. Massive bacterial infection can be identified by bacterial culture, and minimal infection can be detected by molecular pathological methods. These processes include specific enrichment of bacterial and fungal DNA, amplification, and identification of the DNA by gel electrophoresis, sequencing techniques, and chip technologies.Anamnesis (enteral or urogenital infection), the clinical picture (oligoarthritis), and further parameters (e.g., HLA B27 status) are important for the diagnosis of reactive arthritis. In many cases of reactive arthritis, molecular methods allow detection of bacterial DNA or RNA in synovial fluid or tissue. Molecular pathological methods allow the fast and reliable differential diagnosis of granulomatous synovialitis without prior cultivation of bacteria or fungi. The development of new molecular pathological methods for detecting bacterial and fungal nucleic acids will increase diagnostic accuracy.