Periprosthetic joint infections (PJIs) are a dangerous complication of joint replacement surgeries which have become much more common in recent years (mostly hip and knee replacement surgeries). Such a condition can lead to many health issues and often requires reoperation. Staphylococci is a bacterial group most common in terms of the pathogens causing PJIs. S. aureus and coagulase-negative staphylococci are found in around two-thirds of PJI cases. Recently, the numbers of staphylococci that cause such infections and that are methicillin-resistant are increasing. This trend leads to difficulties in the treatment and prevention of such infections. That is why MRSA and MRSE groups require extraordinary attention when dealing with PJIs in order to successfully treat them. Controlling carriage, using optimal prosthetic materials, and implementing perioperative antimicrobial prophylaxis are crucial strategies in infection prevention and are as essential as quick diagnosis and effective targeted treatment. The comprehensive professional procedures presented in this review show how to deal with such cases.