In this article, we address the issue of targeted instruction on interpretive contrasts between native and second-language grammatical meanings. Such mismatches are predicted to create challenges for learners. We illustrate this with French and English pronouns. In French, clitic pronouns (le, la) point to human as well as inanimate referents, while English pronouns distinguish between human (him, her) and inanimate (it) referents. While other grammatical differences between English and French pronouns are taught, this interpretive mismatch attracts less attention in instructional materials. We review the pedagogical literature and report the results of a study investigating this knowledge in Anglophone learners of French as a second language (L2). We document that the mismatch is indeed challenging, particularly to beginning learners, and propose ways to overcome this difficulty.