The marine natural product (-)-palauamine from the sponge Stylotella aurantium represents one of the toughest challenges to total synthesis. It possesses a strained hexacyclic skeleton which leads current methods of organic synthesis to their limit. Recently, several research groups have undertaken independent approaches, focussing on possibly biomimetic approaches involving the underlying biogenetic key metabolite oroidin. Oroidin is the parent compound of the pyrrole-imidazole alkaloids. In this review, recent developments in the field since 2003 are discussed, outlining progress on the dimerization of 4(5)-alkenylimidazoles, total syntheses of non-cyclized pyrrole-imidazole alkaloids, of dibromophakellstatin, agelastatin, and an update on hymenialdisine. Although palauamine has not yet been synthesized, there are original approaches to the system which have afforded biologically active, smaller pyrrole-imidazole alkaloids such as dibromophakellstatin and agelastatin A.