This study reports on the development of an assessment to measure bilingual adolescents' knowledge of polysemous vocabulary and explores the contribution of polysemous word knowledge to reading comprehension among those students. Spanish-English bilingual students in seventh grade (n = 107) completed a battery of standardized reading and language measures along with a researcher-designed measure of their knowledge of the academic senses of words that also have casual, everyday meanings. Item-response theory analyses and correlational analyses provided validity evidence for the assessment. Regression analyses indicated that students' knowledge of academic senses of polysemous words predicted their reading comprehension, even after controlling for their knowledge of the casual sense of the same words, vocabulary breadth, and decoding skills. Findings suggest that comprehension of grade-level texts is uniquely predicted by the ability to recognize the meanings of familiar words when they appear in academic contexts.