In this paper, we examine the nature of interest in science as represented in the Programme for International Student Assessment (PISA) 2006 data. We discuss the interconnections between measures of knowledge, affect, and value as components of interest in science. Working from a perspective acknowledging that many of the models of motivation represented in the literature have been developed in Western countries, we investigated whether the ways that knowledge, affect, and value combine in the structure of students’ interest in science might vary in line with historical and cultural traditions. Four countries were chosen to represent contrasting cultural values as defined in analyses of the World Values Surveys and the European Values Surveys—Colombia, Estonia, USA, and Sweden. Models are described showing variations in fit across the four countries. Efforts to increase the attractiveness of science to students should take heed of the fact that all models indicated a central role for enjoyment of science in the paths linking personal value, interest, and current science activities with intentions for future participation in science. Differences in the strength of the associations between science knowledge and interest in science support the proposition that the interconnections between knowledge, affect, and value need to be understood in relation to students’ broader historical and cultural context.