Measuring chemical exposure is extremely challenging due to the range and number of anthropogenic molecules encountered in our daily lives, as well as their complex transformations throughout the body. To broadly characterize how chemical exposures influence human health, a combination of genomic, transcriptomic, proteomic, endogenous metabolomic, and xenobiotic measurements must be performed. However, while genomic, transcriptomic, and proteomic analyses have rapidly progressed over the last two decades, advancements in instrumentation and computations for nontargeted xenobiotic and endogenous small molecule measurements are still greatly needed.