Research shows that learners of all ages have difficulties deploying key cognitive and metacognitive self-regulatory skills during learning about complex and challenging topics when using open-ended learning environments such as hypermedia. This article provides an overview of the research my students and I have conducted on how the use of self-regulated learning can foster and enhance students' learning about complex science topics using hypermedia. In this article, the term metacognitive tool is used deliberately to highlight (a) the role of metacognitive and self-regulatory processes used by learners during learning and (b) the role of computer environments in prompting, supporting, and modeling students' self-regulatory processes during learning in specific learning contexts (see Azevedo, 2005). I provide an overview of research regarding the use of hypermedia to learn about complex science topics and learning more generally, illustrate how self-regulated learning can be used as a guiding theoretical framework to examine learning with hypermedia, and provide a synthesis of the laboratory and classroom research conducted by our group. Last, I propose several methods for using our findings to facilitate students' self-regulated learning of complex and challenging science topics.