Osteomyelitis and infectious arthritis may lead to permanent sequels and deformities in childhood. It also causes severe morbidity and mortality in other age groups. Microbiological agents leading to orthopaedic infections are various. Aetiological agents may vary depending on the patient`s age, agent`s arrival path to the bone and presence of other underlying diseases. There is a recent increase in prosthetic infections due to the increase of orthopedic implant usage. The exact aetiological factor needs to be isolated and known for accurate antimicrobial treatment. Biopsy of the bone and cultures of the synovial fluid and tissues are important for the diagnosis however swab cultures could be misleading. In cases, where the aetiological agent can not be identified, it is important to estimate and initiate an empirical antibiotic therapy. The pathogenic agents are usually bacteria and the most common one in all age groups is Staphylococcus aureus. Though, in the recent years, Kingella kingae and community acquired Meticilline Resistant Staphylococcus aureus (MRSA) are more commonly isolated. Osteomyelitis and tissue necrosis are common in diabetic foot patients and it usually ends up with amputation of the lower extremity. Initially, most cases are monomicrobial but in the later stages they become polymicrobial. Soft tissue infections can be encountered through a spectrum of diseases including mild cellulitis to lethal necrotizing fasciitis or gas gangrane. In this review, we have evaluated the aetiological agents leading to infections of the skeletal system.