Encapsulation of drugs into multivesicular liposomes (DepoFoam) offers a novel approach to sustained-release drug delivery. While encapsulation of drugs into unilamellar and multilamellar liposomes, and complexation of drugs with lipids, resulted in products with better performance over a period lasting several hours to a few days after intravascular administration, DepoFoam-encapsulation has been shown to result in sustained-release lasting over several days to weeks after non-vascular administration. The routes of administration most viable for delivery of drugs via DepoFoam formulations include intrathecal, epidural, subcutaneous, intramuscular, intra-atricular, and intraocular. DepoFoam particles are distinguished structurally from unilamellar vesicles, multilamellar vesicles, and neosomes in that each particle comprises a set of closely packed non-concentric vesicles. The particles are tens of microns in diameter and have large trapped volume, thereby affording delivery of large quantities of drugs in the encapsulated form in a small volume of injection. A number of methods based on a manipulation of the lipid and aqueous composition can be used to control the rate of sustained-release from a few days to several weeks.