Bordetella holmesii, first described in 1995, is believed to cause both invasive infections (bacteraemia, meningitis, endocarditis, pericarditis, pneumonia, and arthritis) and pertussis-like symptoms. Infection with B holmesii is frequently misidentified as being with B pertussis, the cause of whooping cough, because routine diagnostic tests for pertussis are not species-specific. In this Review, we summarise knowledge about B holmesii diagnosis and treatment, and assess research needs. Although no fatal cases of B holmesii have been reported, associated invasive infections can cause substantial morbidities, even in previously healthy individuals. Antimicrobial treatment can be problematic because B holmesii's susceptibility to macrolides (used empirically to treat B pertussis) and third-generation cephalosporins (often used to treat invasive infections) is lower than would be expected. B holmesii's adaptation to human beings is continuing, and virulence might increase, causing the need for better diagnostic assays and epidemiological surveillance.