Individual variation in responses to commonly used tests of anxiety and spatial memory is often reported. While this variation is frequently considered to be 'noise', evidence suggests that it is, at least partially, related to consistent individual differences in behavioral responses (i.e., personality). The same tests used to assess anxiety are often used to profile personality traits, but personality differences are rarely considered when testing treatment differences in anxiety. Focusing on the rat literature, we describe fundamental principles involved in anxiety and spatial memory tests and we discuss how personality differences and housing conditions can influence behavioral responses in these tests. We propose that an opportunity exists to increase stress resiliency in environmentally sensitive individuals by providing environmental enrichment. We conclude by discussing different approaches to incorporating personality measures into the design and analysis of future studies; given the potential that variation masks research outcomes, we suggest that a strategy which considers the individual and its housing can contribute to improving research reproducibility.