The marine sponges are the source of a unique group of natural products featuring a novel skeleton, the two indole rings were directed linked by a central heterocyclic moiety. Since topsentin, a bis(indolyl)imidazole, and its analogues were isolated from Topsentia genitrix about a decade ago, scientists have isolated various novel bis(indole) alkaloids from marine organisms especially from deep-water sponges in succession. Over the last 15 years there has been an ever-increasing interest in the biological activity of these molecules. These studies became possible as a result of the scientific development of isolation, purification and total synthesis methods concomitant with the development of fairly simple in vitro tests. This paper offers a general view of the recent progress in the field of novel marine bis(indole) alkaloids, including the topsentins, nortopsentins, rhopaladins, hamacanthins, and dragmacidins family natural products. It focuses on the isolation, structure determination, and total synthesis of these bioactive alkaloids.