Macropinocytosis is a form of endocytosis in which cells ingest extracellular fluid and solutes into relatively large endocytic vesicles called macropinosomes. The membrane of macropinosomes derives from plasma membrane following protrusive movements of actin-rich membrane folds called ruffles, which close at their distal margins to enclose extracellular fluids. Nascent macropinosomes either recycle to the cell surface or are delivered into lysosomes, where the enclosed solutes may be degraded by acid hydrolases and transported into the cytoplasm for anabolic metabolism. In some cells, macropinocytosis occurs continuously whereas in others it is initiated by receptor–ligand interactions at the cell surface. A growing number of cellular activities and pathologies have been attributed to macropinocytosis, and additional roles for micropinocytosis in cell physiology remain possible and untested. Therefore, this is a good time to review current understanding of its mechanism, regulation and relevance to physiology and disease. The articles of this issue of Philosophical Transactions B grew out of a discussion meeting entitled, ‘Macropinocytosis’, held in May 2018 and sponsored by the Royal Society. In this introductory article, we summarize current research on macropinocytosis, suggest areas for future work and guide readers to more in-depth reviews of these topics in this special issue or elsewhere in the literature.