Enantiomers of chiral contaminants can significantly differ in environmental fate as well as in effects. Despite this fact, such differences are often ignored in regulation and in practice, injecting uncertainty into the estimation of risk of chiral compounds. We review the unique challenges posed by stereochemistry to the ecological risk assessment of chiral contaminants and existing regulatory guidance for chiral pharmaceuticals and pesticides in the United States. We identify the advantages of obtaining data on fate and effects of each individual enantiomer of chiral contaminants that are either distributed as or may end up as enantiomer mixtures in the environment due to enantiomerization. Because enantiomers of the same compound are highly likely to coexist in the environment with each other and can result in nonadditive effects, we recommend treatment of enantiomers as components of a mixture using widely accepted mixture models from achiral risk assessment. We further propose the enantiomer hazard ratio for retrospectively characterizing relative enantiomer risk and examine uncertainty factor magnitudes for effects analysis.