The usefulness of nanotechnology nowadays in improving the performance of different active pharmaceutical ingredients (API) has generated a great deal of excitement worldwide. These nano-systems offer the advantage of higher bioavailability, lower toxicity, and the ability to deliver drugs with low half-life or low permeability. Lipid nano-based carriers have been extensively used for their ability to protect the API from degradation and their safety as these used lipids are generally regarded as safe. Lipospheres and Pro-nanolipospheres are among the promising systems for the delivery of water-insoluble drugs. They are composed of aqueous dispersible particles with a rigid hydrophobic lipid centre, coated by an outer protective phospholipid exterior. These lipospheres and Pro-nanolipospheres have the advantage of being easy to scale up, high dispersibility in aqueous media, and improved physical stability, making them the perfect candidate for the delivery of different APIs using different routes including oral, parenteral, intranasal and topical routes.