This paper discusses three relationships between content and language integrated learning (CLIL) research and practice in the context of South America. The first relationship focuses on research with successful results in the areas of language learning motivation and intercultural communicative competence and citizenship. The second relationship discusses research which has yielded mixed results to support language learning and cognitive development. The last relationship suggests what areas deserve special attention to offer further support to teachers involved in CLIL provision. The following areas are addressed: teacher-made CLIL materials, language and content gains, L1-L2 (first language, second language) curriculum design, and inclusion. In conclusion, I assert that CLIL in South America can be invigorated if researchers and educators carry out research, preferably in collaboration, that recognises, maximises and improves CLIL in practice. I also suggest that the CLIL community in South America may engage in creating CLIL models and conceptual frameworks that respond to the particularities of their settings with the aim of making CLIL context-responsive and sustainable.