A gender gap persists in the fields of science, technology, engineering, and mathematics (STEM). Although females constitute half the total workforce in the United States, they make up just greater than a quarter of employees in STEM fields. In recent years, one approach to addressing the gender gap in STEM has involved middle grades science teachers helping young adolescent females view themselves as potential scientists from a young age. Through a variety of targeted strategies, science teachers have supported female students in building STEM self-efficacy by encouraging their participation in varied initiatives. This qualitative multi-case study investigated how two middle grades science teachers build STEM self-efficacy in female students both during and outside of formal instruction. Data sources included surveys, interviews, and classroom artifacts. Findings featured specific examples of classroom initiatives that participants believed built female students' self-efficacy as well as participants' reasoning for the initiatives' use and perceived outcomes of their utility. Our findings also indicated that participants' efforts to build female students' STEM self-efficacy were hampered by participants' lack of clarity regarding the meanings of STEM education and STEM self-efficacy. Implications for middle grades teacher education and STEM-focused professional development are included.