The build-up of free fatty acids in non-adipose tissues can result in programmed cell death (PCD), which is thought to contribute to the etiology of diabetes mellitus, cardiomyopathy and other disorders. In mammals, the signalling pathways that mediate apoptosis and other forms of PCD are highly complex – consequently, yeast (which undergoes a form of cell death that is similar in several respects to apoptosis in mammalian cells) has emerged as a model for the study of PCD. Most studies have focused on Saccharomyces cerevisiae but, on page 2671, Hongyuan Yang and colleagues use the fission yeast Schizosaccharomyces pombe to investigate lipid-induced cell death. Using a triacylglycerol-deficient S. pombe mutant, which readily undergoes PCD in response to lipids, the authors identify three distinct lipotoxic cell-death pathways in fission yeast, one of which displays apoptotic nuclear morphology. Notably, the authors show that mitochondria and reactive oxygen species are important in lipotoxic cell death, just as they are in apoptosis in mammalian cells. In addition, they identify several novel cell-death regulators, including the metacaspase Pca1. Their results shed light on the mechanism of lipotoxicity, and establish S. pombe as a model organism for the study of PCD.