Abstract: The state of education in the United States, particularly in the areas of science, mathematics and technology, has been a consistent source of concern since at least the early 1980s when student performance on the 1986 National Assessment of Educational Progress (NAEP) revealed that science proficiency was lower than comparable measures from the 1970's (Alvarado, 1994). For many students, science education continues to be presented primarily through didactic lectures and rote memorization of information. These outdated modes of teaching create un-motivating learning contexts that can significantly impede learner development of deep conceptual understandings (Barab, Sadler, Heiselt, Hickey & Zuiker, 2007). Researchers, teachers and parents are looking for strategies and technologies that create opportunities for students to not just learn the basic principles of science but understand the relationships that govern these principles and their applications. Science is based on inquisitive, collaborative and disciplined investigation in which individuals, and the groups they form, critically analyze the nature of how and why things work. Problem-Based Learning (PBL) is an instructional strategy that supports this perspective on science education. PBL facilitates learner development of collaborative, problem solving skills and promotes scientific reasoning (Barrows, 1996). In this article, we extend the links between science education and PBL to consider computer-based gaming. We examine the use of gaming as a delivery method for PBL opportunities and suggest biotechnology applications as one area of content for game-based PBL. In the final section we introduce Mission Biotech, a game that we have recently developed, as an example of using gaming as a context for PBL. Key words: problem-based learning, PBL, problem solving, scientific reasoning, computer-based gaming, biotechnology Introduction The state of education in the United States, particularly in the areas of science, mathematics and technology, has been a consistent source of concern since at least the early 1980s when student performance on the 1986 National Assessment of Educational Progress (NAEP) revealed that science proficiency was lower than comparable measures from the 1970's (Alvarado, 1994). Throughout the 1990's and 2000' s, science proficiency as measured through NAEP has remained startlingly low (U.S. Department of Education). A 2008 Brookings Institute Report, "Changing the Game: The Federal Role in Supporting 21st Century Educational Innovation," on education reform in the 21st century points to trends among U.S. students in educational attainment placing them far below that of their peers in industrialized nations. Results from recent international comparative assessments, including TIMSS and PISA, (Organisation for Economic Co-operation and Development, 2010) rank U.S. student performance in science around the overall average for industrialized nations and significantly below the highest performing nations. Other reports also lament the lack of success in science and mathematics of many students and cite these issues as among the most significant, long-term economic challenges for the nation (Fleischman, Hopstock, Pelczar & Shelley, 2010). For many students, science education continues to be presented primarily through didactic lectures and rote memorization of information. These outdated modes of teaching create unmotivating learning contexts that can significantly impede learner development of deep conceptual understandings (Barab, Sadler, Heiselt, Hickey & Zuiker, 2007). Researchers, teachers and parents are looking for strategies and technologies that create opportunities for students to not just learn the basic principles of science but understand the relationships that govern these principles and their applications. Science is based on inquisitive, collaborative and disciplined investigation in which individuals, and the groups they form, critically analyze the nature of how and why things work. …