Quinolactacins are a small group of structurally related alkaloids containing an N-methyl pyrroloquinolone skeleton, which were initially identified in the fermentation broth of entomopathogenic Penicillium sp. EPF-6 (isolated from the larvae of the mulberry pyralid, Margaronia pyloalis Welker). These previously unknown and enantiomeric or diastereomeric structures were initially found to inhibit tumor necrosis factor production, but subsequent studies revealed that quinolactacins also act as acetylcholinesterase (AChE) inhibitors. The chemical novelty and relevant biological activity of quinolactacins prompted the development of novel synthetic (and stereoselective) strategies to produce these challenging structures, instead of isolating them from natural sources. This chapter covers all the existing research (from 2000 up to the present), describes novel, naturally occurring quinolactacins, and reports major advances for the partial and total synthesis of this group of compounds. Additional emphasis will be placed on the biological activity of quinolactacins, when available. © 2019 Elsevier B.V.