The sorbicillinoids are a family of hexaketide metabolites that have been isolated from a variety of fungal sources, collected from both marine and terrestrial sources. Since 1948, the family has grown in size to include over 50 members, many of which have complex, highly oxygenated, bicyclic and tricyclic frameworks. In conjunction with their biological activity, the structural complexity of these structures has inspired several synthetic campaigns and has also led to controversy surrounding the biosynthetic pathway responsible for the natural production of these compounds. Through this review, we aim to give a historical perspective to each of these areas and hope to inspire new avenues of research for addressing the knowledge gaps that still exist.