The challenge in chemistry courses for non-science majors (such as nursing majors) is not that the students cannot learn chemistry but that they think they cannot learn chemistry. With this in mind, the authors’ goal was to create a learning environment in which students would feel motivated to learn and would gain confidence in their ability to learn chemistry. In the one-semester chemistry courses for nursing majors described here, health-related scenarios (such as IV therapy, diabetes, blood chemistry, and brachytherapy) provide context, and POGIL activities provide process and content in a cooperative learning environment. In addition, strategic organization and alignment of learning outcomes helps students to focus on the concepts, principles, and theories that they are expected to learn in a meaningful way. Also essential for the success of this course is a caring yet rigorous instructor who effectively communicates that learning chemistry is difficult but doable. This combination of health-related scenarios, POGIL activities, clear learning outcomes, and a supportive instructor gives students hope that they will succeed in their introductory chemistry course and increases their self-concept in chemistry. Chemistry Self-Concept Inventory data collected during 10 semesters at two different universities show a significant positive increase in our students’ chemistry self-concept. Furthermore, Student Assessment of their Learning Gains data collected during the same time period show that students find this learning environment conducive to learning.