This chapter presents chemotaxonomic compilation of protoberberine alkaloids, 13C NMR data of the protoberberine alkaloids and discusses biological activity of the protoberberine alkaloids. The protoberberine alkaloids are comprised of a tetracyclic ring system, which is based on the dibenzo[a,g]quinolizidine system. These tetracyclic alkaloids are derived from benzylisoquinolines through phenolic oxidation and coupling with the isoquinoline N-methyl group, which becomes the ‘‘berberine bridge’’ carbon. This group of alkaloids consists of a series of variations of the main tetracyclic ring system. The most commonly found are: the protoberberines (sensu strictu), such as berberine; the tetrahydroprotoberberines, such as tetrahydropalmatine; and 14-oxo derivatives, such as cryptopine. It was observed that some protoberberine alkaloids act against some pathogenic agents, with very important activities such as antiparasitic, antitrypanosomal, and antileishmaniasis. Other very important biological activities are observed on different specific organic systems. Activities such as analgesic, anticonvulsant, antiamnesic, narcotic, antiarrhythmic, antihemorrhagic, hypotensive, antiinflammatory, antioxidant, antitumoral, antidiarrhetic, antiulcer, smooth muscle relaxant, not to mention many other important activities, are found for this class of alkaloids.