SLNs are primarily composed of solid lipids, which thus impart to SLNs some fundamental properties of lipids, including biocompatibility, biodegradability and low toxicity. SLNs represent a unique class of colloidal drug delivery systems that possess the advantages of both the “soft” drug carriers such as emulsions and liposomes and the solid particles like polymeric nanoparticles. In this review, we will provide an overview on the absorption, disposition and pharmacokinetics of SLNs. The lipidic nature, as well as the relatively small particle size, of SLNs ensures sufficient affinity with the biomembranes, and results in improved absorption via the oral, transdermal, pulmonary, nasal, ocular, rectal or buccal route. One special aspect of oral administration of SLNs is to enhance lymphatic absorption by either the chylomicron-association pathway or the M cell uptake pathway. SLNs for intravenous injections are predominantly captured by liver and spleen. Modification of SLN surface with PEG chains will mask the hydrophobic surface and divert SLNs away from the macrophages that reside in liver and spleen, while ligand-modification will achieve active targeting to specific tissues or organs. Degradation of SLNs is primarily related to lipase-mediated degradation of the lipids themselves.