Many students graduate from K-12 mathematics programs without flexible, conceptual mathematics knowledge. This article reviews psychological and educational research to propose that refining K-12 classroom instruction such that students draw connections through relational comparisons may enhance their long-term ability to transfer and engage with mathematics as a meaningful system. We begin by examining the mathematical knowledge of students in one community college, reviewing results that show even after completing a K-12 required mathematics sequence, these students were unlikely to flexibly reason about mathematics. Rather than drawing relationships between presented problems or inferences about the representations, students preferred to attempt previously memorized (often incorrect) procedures (Givvin, Stigler, & Thompson, 2011; Stigler, Givvin, & Thompson, 2010). We next describe the relations between the cognition of flexible, comparative reasoning and experimentally derived strategies for supporting students' ability to make these connections. A cross-cultural study found that U.S. teachers currently use these strategies much less frequently than their international counterparts (Hiebert et al., 2003; Richland, Zur, & Holyoak, 2007), suggesting that these practices may be correlated with high student performance. Finally, we articulate a research agenda for improving and studying pedagogical practices for fostering students' relational thinking about mathematics. (Contains 4 figures.)