One of the biggest challenges confronting the contemporary drug delivery science today is to improve on the oral bioavailability of a vast number of drugs exhibiting poor and inconsistent gastrointestinal absorption. Self-emulsifying drug delivery systems (SEDDS) have been proved as highly useful technological innovations to surmount such bioavailability hiccups by virtue of their diminutive globule size, higher solubilization tendency for hydro-phobic drugs, robust formulation advantages, and easier scalability in the industrial milieu. Besides, these systems are also known to inhibit the P-glycoprotein (P-gp) efflux, reduce metabolism by gut Cytochrome P-450 enzymes, and circumnavigate the hepatic first-pass effect, facilitating absorption of drugs via intestinal lymphatic pathways. In the last two decades, the phenomenal success of SEDDS as a potential tool for oral delivery of drugs has extrapolated their applications to non-oral delivery also. Various innovative approaches and patented techniques have been reported on formulation of diverse oral and non-oral self-emulsifying (SE) systems not only of various synthetic and semisynthetic drugs, but also of several phytopharmaceuticals, nutraceuticals, and biological macromolecules. Of late, an escalating number of reports have been pouring in on special types of SE systems, mostly nanosized, employing functional excipients such as polar lipids, phospholipids, cellulosic polymer, diblock polymers, etc. This review paper provides an updated bird's-eye view account on the publications and patents of such novel SE approaches for use in both oral and non-oral therapeutics. Providing a relatively pithy overview, this paper thus endeavors to act as a repertoire of knowledge and know-how to guide the product development scientist in formulating variegated SE systems.