Solid lipid nanoparticles (SLNs) are produced from physiologically biocompatible lipids. They have been proven to improve solubility, cellular uptake, and stability, reduce enzyme degradation, and prolong the circulation time of various drugs. SLNs have been applied in the oral, parenteral, transdermal, intranasal, ocular, and pulmonary drug delivery of different drugs, with enhanced safety, bioavailability, and overall therapeutic effects. In this entry, the authors summarize the primary features of SLNs, methods to prepare SLNs, and recent applications of SLNs in drug delivery. Owing to their advantages, SLNs are potential drug delivery systems to improve the management of various diseases and will, soon, be available for clinical use.