Most of the previous problem-based learning (PBL) studies have been conducted with gifted or regular education students and have shown successes. However, little research on PBL exists for disadvantaged middle school students, especially students who are considered to be at risk of failing academically. In this study, we examined the use of a multimedia-enriched PBL science environment by at-risk middle school students. The results, using a mixed-methods design, showed that these students significantly improved their science knowledge and attitude toward science after they engaged in PBL learning. While there were no differences in the scores between the genders, the gain scores from pre- to post-tests in science knowledge and attitude toward science for the girls were larger. A strong positive relationship between attitude toward science and science knowledge was also found. Such research should provide much needed insights on the effect of PBL for all students, not only the gifted but also the underrepresented populations.