The Programme for International Student Assessment (PISA) has been developed by the Organisation for Economic Co-operation and Development to provide participating nations with internationally comparative mean literacy scores in reading, mathematics, and science for students nearing the end of compulsory schooling. The number of nations from the Americas that are participating in PISA has been increasing over the past 4 administrations. This 2-part paper (a) outlines the reaction to PISA within the media of both North and South America and (b) presents an Americas-specific example of the ways in which the PISA dataset can be used for more exploratory analysis through the lens of policy and curriculum suggestions, rather than just league table comparisons. We used multilevel modeling of scientific literacy predicted on a number of school-level background variables. Results point to the importance of socioeconomic background of the student as well as the school in predicting scientific literacy across all nations in the study; however, other school-level significant predictors were more nation-specific. Interpretations of these models as well as next steps are discussed.