The glycoalkaloid saponin alpha-tomatine is a tomato-specific secondary metabolite that accumulates to millimolar levels in vegetative tissues and has antimicrobial and antinutritional activity that kills microbial pathogens and deters herbivorous insects. We describe recent insights into the biosynthetic pathway of alpha-tomatine synthesis and its regulation. We discuss the mode of action of alpha-tomatine by physically interacting with sterols, thereby disrupting membranes, and how tomato protects itself from its toxic action. Tomato pathogenic microbes can enzymatically hydrolyze, and thereby inactivate, alpha-tomatine using either of three distinct types of glycosyl hydrolases. We also describe findings that extend well beyond the simple concept of plants producing toxins and pathogens inactivating them. There are reports that toxicity of alpha-tomatine is modulated by external pH, that alpha-tomatine can trigger programmed cell death in fungi, that cellular localization matters for the impact of alpha-tomatine on invading microbes, and that alpha-tomatine breakdown products generated by microbial hydrolytic enzymes can modulate plant immune responses. Finally, we address a number of outstanding questions that deserve attention in the future. CI - (c) 2020 The Authors New Phytologist (c) 2020 New Phytologist Foundation.