Replacement of large joints in the lower limbs is a commonly accepted and used method for the treatment of osteoarthritis. Like any other intervention, this treatment method also involves the risk of complications. Periprosthetic joint infection is one of the most serious ones. It qualifies patients for further procedures, which significantly impairs their daily activity and the comfort of life. Osteoarticular infections represent a major therapeutic challenge. This is associated with both, poor penetration of antibiotics into the osteoarticular compartment (system) as well as with the increasing drug resistance of pathogens. Osteoarticular infections require several weeks of antibiotic therapy, as an adjunct treatment, which is an additional financial burden. The implementation of primary prevention scheme in periprosthetic joint infection allows for a significant reduction in the risk of this complication. The article discusses the different nature of the infection within joints and orthopaedic implants. We have presented the key principles for the prevention of septic complications associated with total hip and knee replacement, by discussing the most common sources of primary infection. We have proposed a treatment algorithm based on diagnostic tests reducing the risk of infectious complications and increasing the safety of surgical intervention (surgical procedure) as well as the chances for good long-term treatment outcomes.