Nanoscale oil-in-water emulsions (NEs), heterogeneous systems of two immiscible liquids stabilized by emulsifiers or surfactants, show great potential in medical applications because of their attractive characteristics for drug delivery. NEs have been explored as therapeutic carriers for hydrophobic compounds via various routes of administration. NEs provide opportunities to improve drug delivery via alternative administration routes. However, deep understanding of the NE manufacturing and functionalization fundamentals, and how they relate to the choice of administration route and pharmacological profile is still needed to ease the clinical translation of NEs. Here, we review the diversity of medical applications for NEs and how that governs their formulation, route of administration, and the emergence of increasing sophistication in NE design for specific application.