Staphylococcus aureus and Streptococcus pyogenes are important contributors to disease in northern Australia. Both are opportunistic pathogens, frequently carried on the skin or in the respiratory tract in the absence of disease. A large proportion of the S. aureus strains causing infection in northern Australia possess the Panton Valentine (PVL) toxin, with ST93, ST5, and ST121 being significant. PVL+ strains are associated with both community- and healthcare-associated infections, and a large proportion are methicillin-resistant S. aureus (MRSA). MRSA strains known to be healthcare associated (ST239 and ST22) are not prevalent. CC1 PVL− MRSA continue to cause infections. The diversity of S. pyogenes emm types in northern Australia is high with skin tropic and non-tropic emm types predominating. This contrasts with other parts of Australia where emm diversity is lower and rates of pharyngitis higher. The high diversity raises concerns for the likely efficacy of vaccines based on the variable region of the M protein, the nucleotide sequence of which underpins emm typing. It is likely that complex interactions occur between these two important bacterial pathogens, and other important skin pathogens in the region such as the scabies mite.