The BSCS 5E Instructional Model, an elaboration of the well-known and accepted three-part learning cycle, is a five-part approach to incorporating inquiry-based, active learning in the classroom. Developed in 1987 by the Biological Sciences Curriculum Study, "the 5Es" is a popular K-20 instructional practice, and as such, the Biological Sciences Curriculum Study has advocated for the empirical study of its effectiveness. We present a systematic review of English-language peer-reviewed publications of empirical studies of the 5Es for K-20 mathematics and science teaching and learning. We report our search process and analyses, revealing the characteristics of the literature found that specifically question the effectiveness of the 5Es: 45 articles have been published, beginning in 2006, in 33 journals. Of those with scores available, the average SCImago Journal & Country Rank was 0.587, and the average Impact Factor was 1.151 for year of publication. From our synthesis, we find that the 5Es are more impactful than traditional instruction, yet comparisons of the 5Es to the original learning cycle predecessor have not been done, and the 5Es are not necessarily more effective than other inquiry methods. While dosage does not seem to matter in the studies in our corpus, the 5Es are particularly studied and found to be positively impactful in secondary biology contexts. The relatively few studies with teachers and students in mathematics contribute to both a nuanced understanding of some limitations of the rest of the data corpus and are areas for future research.