Recent progress in the synthesis and investigation of the biological activities of cyclopeptide alkaloids is reviewed. New strategies have been devised to overcome some of the synthetic challenges inherent in the formation of strained paracyclophanes. However, issues remain which offer opportunities for the application of catalytic enantioselective organometallic reactions. Members of this class of natural products have been isolated from various parts of a wide variety of plants and researchers will likely continue to show great interest in their formation and function. The biological properties of certain members of this class warrant further investigation. To gain additional insight into these areas, continuing development of synthetic methodology will be essential.