Oxygen heterocycles are the second most common type of heterocycles that appear as structural components of U.S. Food and Drug Administration (FDA) approved pharmaceuticals. Analysis of our database of drugs approved through 2017 reveals 311 distinct pharmaceuticals containing at least one oxygen heterocycle. Most prevalent among these are pyranoses, with furanoses, macrolactones, morpholines, and dioxolanes rounding off the top five. The main body of this Perspective is organized according to ring size, commencing with three- and four-membered rings and ending with macrocycles, polymers, and unusual oxygen-containing heterocycles. For each section, all oxygen heterocycle-containing drugs are presented along with a brief discussion about structural and drug application patterns.