Clinicians frequently request serologic tests to provide evidence of prior infection by Streptococcus pyogenes, especially when suspecting a diagnosis of acute rheumatic fever or post-streptococcal glomerulonephritis. However, the interpretation of these tests is difficult and should take account of the clinical features, epidemiological setting, and pre-test probability, as well as the specific aspects of the assay. This review details the characteristics of streptococcal serologic assays and provides recommendations for their use and interpretation.