Apoptosis is a physiological form of cell death. Cells undergoing apoptosis execute a genetically controlled program that leads to organized breakdown of cellular structures and ends in phagocytosis of their remains. In mast cells, several mechanisms regulating apoptosis have been identified including growth factors, tumor necrosis factor-alpha receptors, monomeric IgE, Toll-like receptors, and proteins of the bcl-2 family. Methods used to characterize apoptosis of mast cells are reviewed, with special attention to flow cytometric analysis of annexin V staining, analysis of deoxyribonucleic acid fragmentation by gel electrophoresis and end-labeling techniques, measurement of caspase activity by enzymatic assays, and characterization of pro- and anti-apoptotic proteins by immunoblotting.