We present a guided-inquiry biology lesson, using the plant–rhizobium symbiosis as a model system. This system provides a rich environment for developing connections between the big ideas in biology as outlined in the College Board’s new AP Biology Curriculum. Students gain experience with the practice of scientific investigation, from designing and conducting experiments to making claims based on the data they collect. We include one example of a piloted classroom experiment that can easily be modified to test a variety of interesting ecological and evolutionary hypotheses.