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A burdensome, atypical phenotype of Staphylococcus aureus (SA) called SA small colony variants (SCVs) has been identified, which is induced because of a combination of environmental stressors, including polymicrobial interactions. SA-SCVs exhibit altered phenotypes because of metabolic dormancy caused by electron-transport deficiency, which leads to increased biofilm production and alterations to antimicrobial susceptibility. SA-SCVs typically exhibit altered colony morphology and biochemical reactions compared with wild-type SA, making them difficult to detect via routine diagnostic procedures. SA-SCVs have been found to contribute to chronic or recurrent infections, including skin and soft-tissue infections, foreign-body-associated infection, cystic fibrosis, and sepsis. There is evidence that SA-SCVs contribute to patient morbidity and mortality rates because of diagnostic difficulties and limited treatment options. New detection methods may need to be developed that can be incorporated into routine diagnostic procedures, which would allow for better assessment of specimens and introduce new considerations for management.