Besides their essential role in the immune system, sphingolipids and their metabolites are potential key regulators in the life cycle of obligatory intracellular pathogens such as viruses. They are involved in lateral and vertical segregation of receptors required for attachment, membrane fusion and endocytosis, as well as in the intracellular replication, assembly and release of viruses. Glycosphingolipids may themselves act as receptors for viruses, such as Galactosylceramide for human immunodeficiency virus (HIV). In addition, sphingolipids and their metabolites are inseparably interwoven in signal transduction processes, dynamic alterations of the cytoskeleton, and the regulation of innate and intrinsic responses of infected target cells. Depending on the nature of the intracellular pathogen, they may support or inhibit infections. Understanding of the underlying mechanisms depending on the specific virus, immune control, and type of disease may open new avenues for therapeutic interventions.