Background. The ability to adaptively transfer acquired fear to novel situations is fundamental for survival in ever-changing environments and may contribute to the emergence and persistence of anxiety disorders. Consequently, research has focused on the assessment of fear generalization profiles to predict individual differences in anxiety. However, substantial heterogeneity in the operationalization of generalization hampers comparisons across studies and poses a risk to the replicability of findings. Methods. To address these issues, we reviewed the literature to identify commonly used methods for characterizing perceptual fear generalization profiles. Then, we conducted simulation analyses to examine correlations between indices and probe their robustness against measurement noise. Finally, we used 2 large empirical datasets (N = 1175 and N = 256 healthy humans) to examine the reliability of these indices and their validity in predicting anxiety-related traits. Results. All identified indices were substantially correlated but highly sensitive to measurement noise, with only minimal differences between methods. Reliabilities were moderate for subjective ratings but poor for skin conductance responses. All indices of fear generalization were unrelated to anxiety-related traits. Conclusions. Overall, a more comprehensive discussion of conceptual and methodological issues is needed to enable informed decisions about how to reliably and validly estimate fear generalization and its relationship with anxiety-related traits or clinical symptoms.