Positive epidemiologic and toxicologic studies underline the need for assessment of human health risks from ubiquitous exposures to mixtures of disinfection by‐products (DBPs). Typical human exposures to DBPs are at extremely low levels; thus, health risk is likely to be attributable to multiple, rather than single, DBP exposures. This article suggests three approaches to evaluating health risks from DBP mixtures: (1) toxicologic studies of simple defined mixtures, (2) toxicologic studies using reproducible disinfection scenario samples, and (3) toxicologic or epidemiologic studies conducted directly on drinking water samples. The authors believe all three approaches are valid and can provide data applicable to DBP risk assessment. They also postulate that single‐chemical toxicologic studies are, by themselves, insufficient to fully characterize DBP health risks. A concentrated effort by a multidisciplinary team of researchers is necessary to generate appropriate DBP mixtures health data.