Short chain carboxylic acids (SCCA) are natural compounds from plants or fermenting microbes that have a long history as natural biopreservatives. This article discusses sources, mode of action and additional compound structures influencing antimicrobial activity. Traditionally, antimicrobial activity of SCCA has been linked to the ability to lower environmental pH and to diffuse into the cell causing intracellular acid stress. Recent studies at controlled pH suggest that antimicrobial activity not only increases with higher pKa and lower pH, but also depends on the compound structure, e.g. presence of hydrophobic or hydrophilic side groups. Exploiting strategies of microbial cross-feeding and metabolism of amino acids could tailor and expand the spectrum of SCCA further, e.g. for application in protein-rich beverages and plant-based milk analogues.