At the University of Pittsburgh, the author and his colleagues have been exploring a range of approaches to design challenges for implementation in high school science classrooms. In general, their approach has always involved students working during class time over the course of many weeks. So, their understanding of what works must be contextualized to that situation (i.e., without significant home support, by students enrolled in traditional classrooms, involving content that is connected to traditional science classrooms). However, their approach has been implemented with thousands of students in over 80 classrooms ranging from 9th grade biology or general science to 11th grade physics, from traditional mainstream science classrooms to elective Biology II or Honors Chemistry, and from high needs urban classrooms to affluent suburban classrooms. In other words, there is some important generality to these experiences. They have also conducted a number of studies on students in these settings, to understand a range of factors that influence student learning and affect outcomes. This white paper provides a brief summary of principles that appear to guide successful experiences for students.