The article provides a comprehensive review of the pathogenesis of *Staphylococcus aureus* infections, with a focus on methicillin-resistant strains (MRSA). It begins by discussing the general aspects of staphylococcal pathogenesis, emphasizing the role of colonization and virulence factors in the development of infections. The article highlights that while MRSA strains are not necessarily more virulent than methicillin-sensitive S. aureus (MSSA) strains, certain MRSA strains may possess factors or genetic backgrounds that enhance their virulence or enable them to cause specific clinical syndromes. The review then delves into the pathogenesis of hospital-acquired MRSA (HA-MRSA) and community-acquired MRSA (CA-MRSA). HA-MRSA infections are often caused by internationally disseminated clones, such as the Iberian, Brazilian, Hungarian, New York/Japan, and Pediatric clones. These clones are characterized by their high transmissibility and ability to cause severe infections. The Brazilian clone, for example, has been responsible for invasive staphylococcal infections in Brazil due to its enhanced ability to adhere, persist, and invade host tissues. CA-MRSA infections, on the other hand, have emerged in the community and are often associated with specific clonal strains, such as USA300 and USA400. These strains are highly virulent and have been linked to necrotizing pneumonia and skin and soft-tissue infections. The presence of Panton-Valentine leukocidin (PVL), a toxin that causes leukocyte lysis and dermonecrosis, is a significant factor in the virulence of CA-MRSA strains. However, the role of PVL in staphylococcal virulence remains a subject of debate, with some studies suggesting it is not the primary determinant of disease severity. The article also discusses the genetic and environmental factors that contribute to the spread and virulence of MRSA strains. It highlights the importance of understanding the complex regulation of virulence factors and the role of specific clones in the persistence and transmission of these pathogens. Despite significant progress, many questions remain unanswered, particularly regarding the specific mechanisms by which certain MRSA strains cause more severe infections compared to MSSA. The authors emphasize the need for further research to improve prevention and treatment strategies for staphylococcal infections.The article provides a comprehensive review of the pathogenesis of *Staphylococcus aureus* infections, with a focus on methicillin-resistant strains (MRSA). It begins by discussing the general aspects of staphylococcal pathogenesis, emphasizing the role of colonization and virulence factors in the development of infections. The article highlights that while MRSA strains are not necessarily more virulent than methicillin-sensitive S. aureus (MSSA) strains, certain MRSA strains may possess factors or genetic backgrounds that enhance their virulence or enable them to cause specific clinical syndromes. The review then delves into the pathogenesis of hospital-acquired MRSA (HA-MRSA) and community-acquired MRSA (CA-MRSA). HA-MRSA infections are often caused by internationally disseminated clones, such as the Iberian, Brazilian, Hungarian, New York/Japan, and Pediatric clones. These clones are characterized by their high transmissibility and ability to cause severe infections. The Brazilian clone, for example, has been responsible for invasive staphylococcal infections in Brazil due to its enhanced ability to adhere, persist, and invade host tissues. CA-MRSA infections, on the other hand, have emerged in the community and are often associated with specific clonal strains, such as USA300 and USA400. These strains are highly virulent and have been linked to necrotizing pneumonia and skin and soft-tissue infections. The presence of Panton-Valentine leukocidin (PVL), a toxin that causes leukocyte lysis and dermonecrosis, is a significant factor in the virulence of CA-MRSA strains. However, the role of PVL in staphylococcal virulence remains a subject of debate, with some studies suggesting it is not the primary determinant of disease severity. The article also discusses the genetic and environmental factors that contribute to the spread and virulence of MRSA strains. It highlights the importance of understanding the complex regulation of virulence factors and the role of specific clones in the persistence and transmission of these pathogens. Despite significant progress, many questions remain unanswered, particularly regarding the specific mechanisms by which certain MRSA strains cause more severe infections compared to MSSA. The authors emphasize the need for further research to improve prevention and treatment strategies for staphylococcal infections.