The Author, in this chapter, reports the experience implemented at the reference center of Cortina d’Ampezzo for the diagnosis and treatment of osteoarticular infections by evaluating an experience that takes into consideration a series of pyogenic pathologies of approximately 3700 cases compared with approximately 4000 cases of tuberculous forms. It should also be highlighted that pyogenic septic arthritis is quite rare as many times it involves infections resulting from trauma or postsurgical infections or, sometimes, due to local infiltrations and only rarely you have native pyogenic joint infections. Therefore, we wanted to describe septic arthritis due to tuberculous infection, which instead, most of the time, manifests itself as joint localization, comparing it with pyogenic arthritis. This choice arises from the fact that many times the diagnosis of tuberculous form is neglected leading to unsatisfactory results so as not to define them as disastrous. Localizations affecting the spinal column are excluded from the following treatment. The two pathologies are then compared and contrasted: pyogenic and tuberculous arthritis. The differences are highlighted especially in the anamnestic, clinical, and laboratory aspects to reach the most certain diagnosis possible. Finally, the type of treatment is differentiated, both surgical and antibiotic, presenting both the times and the type of antibiotic notable differences. In the final part of this chapter, clinical cases are reported which highlight the differences and how these should be treated.