During autophagy, portions of the cytoplasm are sequestered into autophagosomes and digested by lysosomal hydrolases. Massive autophagy can be induced in mammalian tissues in a coordinated fashion through nutrient deprivation, which has prompted the search of soluble metabolites that can stimulate autophagy. Ammonia, which is generated as a by-product of glutaminolysis, has been identified as a diffusible factor that stimulates autophagy. Intriguingly, cancer cells increase the rate glutaminolysis and the interstitial fluid of cancers contains higher-than-normal physiological concentrations of ammonia, suggesting a previously unknown pathway through which tumor cells can condition their microenvironment.