Macropinocytosis is a means by which eukaryotic cells ingest extracellular 
liquid and dissolved molecules. It is widely conserved amongst cells that can 
take on amoeboid form and, therefore, appears to be an ancient feature that can 
be traced back to an early stage of evolution. Recent advances have highlighted 
how this endocytic process can be subverted during pathology - certain cancer 
cells use macropinocytosis to feed on extracellular protein, and many viruses 
and bacteria use it to enter host cells. Prion and prion-like proteins can also 
spread and propagate from cell to cell through macropinocytosis. Progress is 
being made towards using macropinocytosis therapeutically, either to deliver 
drugs to or cause cell death by inducing catastrophically rapid fluid uptake. 
Mechanistically, the Ras signalling pathway plays a prominent and conserved 
activating role in amoebae and in mammals; mutant amoebae with abnormally high 
Ras activity resemble tumour cells in their increased capacity for growth using 
nutrients ingested through macropinocytosis. This Commentary takes a functional 
and evolutionary perspective to highlight progress in understanding and use of 
macropinocytosis, which is an ancient feeding process used by single-celled 
phagotrophs that has now been put to varied uses by metazoan cells and is abused 
in disease states, including infection and cancer.