Satiety is a complex state, influenced by numerous factors that go beyond food ingestion. Satiety influences food habits and behavior, thus affecting human health. This review provides an overview of physiological mechanisms involved in satiety and of methodologies to assess food intake and satiety in both animal models and humans. The following topics are highlighted: differences between satiety and satiation; how the central nervous system regulates food intake and satiety; the impact of different macronutrients on satiety; and how the manipulation of food composition might influence overall satiety. Bringing together knowledge on this myriad of satiety mechanisms and how we can study them is useful to better understand and control obesity and other eating disorders.