Sphingolipids (SLs) and ceramides are essential structural components of eukaryotic membranes. In addition, they have begun to find increasingly important roles in various bacteria where evidence suggests they are involved in human/microbe interactions. Many of the enzymes and pathways involved in the key biosynthetic are steps conserved between microbes, yeast, plants and mammals. The eukaryotic homologues are membrane-bound and have been difficult to study, so the soluble bacterial versions have been ideal models to understand the structure, function and mechanisms of key enzymes. One particular focus has been the first enzyme in the pathway, serine palmitoyltransferase (SPT). This catalyses the condensation of L-serine with palmitoyl-CoA to generate the first long chain base intermediate. I will review our detailed analysis of bacterial SPTs and show how they provide excellent models that allowed the determination of the structure of the human SPT complex. I will also present new studies to highlight the potential roles of bacterial SLs in the human microbiome, as well as in pathogenesis.