Scytonemin is a lipid-soluble, highly stable, yellow–brown-coloured secondary metabolite that is accumulated in the extracellular polysaccharide sheath of several but not all members of cyanobacteria. Chemically, scytonemin is an indole alkaloid composed of two heterocyclic units symmetrically connected through a carbon–carbon bond. Thus, scytonemin is unique among natural products due to its special structure, location in a cell, as well as strong absorption maxima in UV-A in addition to the violet–blue region. Traditionally, scytonemin is a well-established photoprotective compound against ultraviolet radiation. Its accumulation in the cyanobacterial sheath has been suggested to be a strategy adopted by several cyanobacteria to protect their cellular components against damaging effects of UVR. Additionally, recent studies have also established the importance of scytonemin in reactive oxygen species scavenging as well as in controlling the growth of cancerous cells. Thus, scytonemin is both ecologically as well as pharmaceutically important metabolite. Recent developments made in the biochemistry and genetics of this compound have paved the way for its application and commercialization for human welfare. This review aims to present a brief history of the compound with chronological developments made in the study of scytonemin and emphasizes its physiochemistry, analytical chemistry, biochemistry, and genetics. We provide a separate section for metabolic engineering and potential applications of scytonemin, mainly as sunscreen and anti-cancerous drugs. We also discuss the future research directions which need to be worked out. © 2019, The National Academy of Sciences, India.