The present review covers the literature on bisbenzylisoquinoline alkaloids from 1999 through early 2018. About 500 natural products belong to this large alkaloid class, of which 65 were characterized for the first time in the period covered by this chapter. The review comprises a classification of bisbenzylisoquinoline alkaloids and gives an overview of the principal biosynthetic pathways. Furthermore, a list of the novel natural products as well as their available analytical data are included in this chapter. Special emphasis is given to the progress in the total synthesis of bisbenzylisoquinoline alkaloids. To accommodate the drastically increased number of publications concerning the biological and pharmacological evaluation, an overview on the most important biological findings is provided. CI - (c) 2019 Elsevier Inc. All rights reserved.