Receptor-mediated cellular events have received major attention in the field of drug/gene delivery in the past few years. These events, which arc mediated through the endogenous ligands/epitopes, could be exploited for designing site-specific and target-oriented delivery systems. The past decade has seen the development of endogenous ligands and their mimics of exogenous origins to selectively deliver the contained or immobilized moieties to the cellular interiors using a wide range of cell surface receptors/epitopes. Ligand-mediated active targeting has emerged as a novel paradigm in targeting either vascular compartment (first-order), cellular (second-order), or intracellular (third-order) levels. Most carrier systems or bioconjugates explored so far can be used as cargo units for the site-specific presentation and delivery of various bioactives using biorelevant ligands, including antibodies, polypeptides, oligosaccharides (carbohydrates), viral proteins, fusogenic residues, and molecules of endogenous origin. In this review, we describe various ligand-receptor systems that have been investigated to date for targeted or cellular drug delivery. These include blood carbohydrate (lectin) receptors, Fc receptors, complement receptors, interleukin receptors, lipoprotein receptors, transferrin receptors, scavenger receptors, receptors/epitopes expressed on tumor cells, and cell adhesion receptors. The role of receptors as molecular target has opened new opportunities for cellular or intra-cellular targeting using carrier systems appended with targeting handles (ligands). Research in the field of ligand-receptor-based targeted system is expected to be an armamentarium and the focal point of research in the next millennium.