It has long been known that fungal pathogens like Fusarium and Alternaria spp. produce toxins (mycotoxin) to kill plant cells. These mycotoxins have been shown to perturb the plant sphingolipid biosynthesis pathway, resulting in the necrotic cell death of plant cells. A recent study by Shi et al. revealed that an increase in the amount of cellular sphingoid bases triggers plant programmed cell death (PCD) through accumulation of reactive oxygen species (ROS). These findings point to the importance of sphingolipids in the regulation of plant cell in disease development as well as in defense responses. In the latest report, we showed that serine palmitoyltransferase (SPT), the key enzyme of sphingolipid biosynthesis, regulates not only plant cell death but also defense response against a non-host pathogen, soliciting further studies to elucidate the roles of sphingolipids in plant innate immunity.