The present minireview aims to provide a context for imagination of the timespan for bone infection evolution from the origin of cellular bone tissue to modern orthopedic surgery. From a phylogenetic osteomyelitis-bracketing perspective, and due to the time of osteocyte origin, bacteria might have been able to infect the skeleton for approximately 400 million years. Thereby, bone infections happened simultaneously with central expansions of the immune system and development of terrestrial bone structure. This co-evolution might aid in explaining the many immune evasion strategies seen in the field of bone infections. Bone infection patients with long disease-free periods followed by sudden recurrence and anamnesis of long-term and low-grade infections indicate that bacteria can perform silent parasitism within bone tissue (parasitism; one organism lives on another organism, the host, causing it harm and is structurally adapted to it). The silence seems to be disturbed by immunosuppression and the present minireview shows that a compromised immune system has been associated with bone infection development across all species in the phylogenetic tree. Orthopedic surgery, including arthroplasty and osteosynthesis, favor introduction of bacteria and prosthesis/implant related infections are thus anthropogenic infections (anthropogenic; resulting from the influence of human beings on nature). In that light it is important to remember that the skeleton and immune system have not evolved for millions of years to protect titanium alloys and other metals, commonly used for orthopedic devices from bacterial invasion. Therefore, these relatively new orthopedic infection types must be seen as distinct with unique implant/prosthesis related pathophysiology and immunology.