The purpose of this study is to review empirical research articles regarding game-based science learning (GBSL) published from 2000 to 2011. Thirty-one articles were identified through the Web of Science and SCOPUS databases. A qualitative content analysis technique was adopted to analyze the research purposes and designs, game design and implementation, theoretical backgrounds and learning foci of these reviewed studies. The theories and models employed by these studies were classified into four theoretical foundations including cognitivism, constructivism, the socio-cultural perspective, and enactivism. The results indicate that cognitivism and constructivism were the major theoretical foundations employed by the GBSL researchers and that the socio-cultural perspective and enactivism are two emerging theoretical paradigms that have started to draw attention from GBSL researchers in recent years. The analysis of the learning foci showed that most of the digital games were utilized to promote scientific knowledge/concept learning, while less than one-third were implemented to facilitate the students’ problem-solving skills. Only a few studies explored the GBSL outcomes from the aspects of scientific processes, affect, engagement, and socio-contextual learning. Suggestions are made to extend the current GBSL research to address the affective and socio-contextual aspects of science learning. The roles of digital games as tutor, tool, and tutee for science education are discussed, while the potentials of digital games to bridge science learning between real and virtual worlds, to promote collaborative problem-solving, to provide affective learning environments, and to facilitate science learning for younger students are also addressed.