This review describes the most recent synthetic routes directed toward the construction of structurally complex indole alkaloids, many syntheses of which contain the asymmetric Pictet-Spengler reaction as a key stereochemical step. A kinetic and conformational study of the epimerization of cis 1,2,3-trisubstituted tetrahydro-beta-carbolines into their trans counterparts is described, because this is key to complete asymmetric induction in the Pictet-Spengler reaction. A mechanistic study of the enzyme-catalyzed Pictet-Spengler reaction is also included. The total synthesis of the opioid agonist mitragynine, as well as corynantheidol and the oxindole alstonisine is presented. With regard to bisindole alkaloids, the total synthesis of the antileishmanial bisindoles accedinisine and N'-demethylaccedinisne is described.