Self-cooling compositions and systems adapted to rapidly chill a substance in a compact container are provided. In some implementations, the composition comprises an aqueous solution and solid chemical reactants, wherein at least one solid chemical reactant is selected independently from the group consisting of NH4NO3, urea, and mixtures thereof; and a second solid chemical reactant is selected independently from the group consisting of NH4Cl, calcium sulfate, borax, phosphates, MgCl2, carrageenan, and mixtures thereof. The self-cooling compositions and systems can have a wide range of applications such as cooling comestibles or medical assay kits.