Abstract. Compound-specific stable isotope analysis (CSIA) of individual amino acids (AAs) has become a powerful analytical tool in trophic ecology. Heavily fractionating "trophic" AAs (e.g., glutamic acid: Glu) provide a robust indicator of trophic transfer, while minimally fractionating "source" AAs (e.g., phenylalanine: Phe) closely reflect the δ 15 N value at the base of the food web (δ 15 N baseline ). Together, the CSIA-AA approach provides an unprecedented ability to disentangle the influences of δ 15 N baseline values and trophic fractionation on consumer nitrogen isotope values. Perhaps the most important assumption underlying CSIA-AA applications to trophic ecology is that trophic fractionation of Glu and Phe, and thus the trophic discrimination factor TDF Glu-Phe (Δ 15 N Glu − Δ 15 N Phe ), is effectively constant across diverse consumer-resource relationships. To test this assumption, we conducted a comprehensive meta-analysis of controlled feeding experiments that examined individual AA trophic fractionation (Δ 15 N C-D ) and resulting TDF Glu-Phe values. We found tremendous variability in TDF Glu-Phe values from 0‰ to >10‰ across 70 species (317 individuals) and 88 distinct consumer-diet combinations. However, this variability appears to follow predictable patterns driven by two dominant variables: diet quality and mode of nitrogen excretion. Consumers feeding on high-quality diets (small diet-consumer AA imbalances) tend to have significantly lower TDF Glu-Phe values than consumers feeding on low-quality diets. Similarly, urea/uric acid-producing consumers also exhibit significantly lower TDF Glu-Phe values than their ammonia-producing counterparts. While these patterns are certainly not universal, together these factors likely explain many of the observed patterns of TDF Glu-Phe variability. We provide an overview of the biochemical and physiological mechanisms underpinning AA Δ 15 N C-D to explain these patterns. There are several seemingly unique systems, including the remarkably consistent TDF Glu-Phe values across insect food webs and the isotopically "invisible" trophic transfers in microbial food webs, that may provide additional insight into the influence of diet quality and nitrogen cycling on AA fractionation. In this review, we argue that to realize the full potential of CSIA-AA approaches in trophic ecology, we must embrace the variability in TDF Glu-Phe values. This likely requires developing new models of trophic transfer dynamics for some applications, including multi-TDF Glu-Phe equations that directly incorporate variability in TDF Glu-Phe value.