Abstract: The present invention relates to cationic ceramides, their dihydro-analogs and aromatic analogs and their derivatives, comprising a pyridinium group. Also provided are methods for making cationic ceramides comprising a pyridinium group, and their use for treating or preventing diseases associated with cell overproliferation and sphingolipid signal transduction, such as cancer, inflammation, and stenosis. The compounds are also useful as mitochondritropic agents that are localized to mitochondria carrying with them chemical cargoes, such as drugs, or signaling molecules, such as fluorophores for probing organelle structure and functions.