This article reviews the most relevant methodological aspects involved in Health Technology Assessment (HTA). Firstly, it addresses the process of defining the research problem (or scoping). Then it explains some specific aspects of systematic reviews of evidence, as well as indirect and mixed comparisons of the effectiveness of interventions. It covers also the methods for economic evaluation in healthcare and the budget impact analysis of interventions. Finally, the paper provides an empirical insight on the methodological emphasis used by HTA agencies around the world, and reflects on the available capacities in our country in the topics discussed.