Fungi are well-known for their abundant supply of metabolites with unrivaled structure and promising bioactivities. Naphthalenones are among these fungal metabolites, that are biosynthesized through the 1,8-dihydroxy-naphthalene polyketide pathway. They revealed a wide spectrum of bioactivities, including phytotoxic, neuro-protective, cytotoxic, antiviral, nematocidal, antimycobacterial, antimalarial, antimicrobial, and anti-inflammatory. The current review emphasizes the reported naphthalenone derivatives produced by various fungal species, including their sources, structures, biosynthesis, and bioactivities in the period from 1972 to 2021. Overall, more than 167 references with 159 metabolites are listed.