Triterpenes are widely found amongst various natural sources and are derived from squalene or related 30-carbon acyclic congeners. Medicinal plants are an excellent source of pharmaceutical agents, and the renewability of these resources renders further significance and importance to the discovery and development of drugs from natural products. Betulin, betulinic acid, and other analogous triterpenoids related to the lupane, oleanane, and ursane families are secondary plant metabolites that are most commonly found in fruit peels, leaves, and stem bark. Betulin and betulinic acid are lupane-type natural products isolated from the bark of yellow and white birch trees. Betulin occurs in > 200 types of plant species with the highest percentage of the natural product of up to 10%–25% composing the outer part of certain types of birch bark. These birch trees are native to North America and several parts of Europe. Betulin is remarkably abundant in nature, which makes it an excellent raw material for the synthesis of the biologically active compounds. This review will cover the latest developments in the design, synthesis, characterization, and medicinal applications of betulin and betulinic acid derivatives, specifically in the areas of cancer and aids.