jats:titleAbstract</jats:title>jats:pThe marine natural product hemicalide displays potent anticancer activity. While detailed NMR experiments established the planar carbon skeleton, its full configurational assignment proved enigmatic. This Review summarises ongoing synthetic efforts and NMR studies on hemicalide, which have succeeded in reducing the number of possible stereoisomers from more than one million to a more manageable eight structures, setting the stage for a focused total synthesis campaign.</jats:p>