The past several years have seen an increase in the discovery and isolation of natural products of the indole alkaloid class. Bis- and tris-indole alkaloids are classes of natural products that have been shown to display diverse, potent biological activities. Of particular interest are bis- and tris-indole alkaloids containing N-heterocyclic linker moieties. It has been reported that more than 85% of biologically active compounds contain one or more heterocyclic moieties; of these, N-heterocycles have been identified as the most prevalent. The goal of this review is to provide a detailed overview of the recent advances in isolation and total synthesis of bis- and tris-indole alkaloids that contain N-heterocyclic linker moieties. The known biological activities of these natural products will also be discussed.