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Sponges are prolific sources of various natural products that have provided the chemical scaffolds for new drugs. The sponges of the genus <i>Petrosia</i> inhabit various regions and contain a variety of biologically active natural products such as polyacetylenes, sterols, meroterpenoids, and alkaloids. This review aims to provide a comprehensive summary of the chemical structures and biological activities of <i>Petrosia</i> metabolites covering a period of more than four decades (between 1978 and 2020). It is also described in this review that the major groups of metabolites from members of the genus <i>Petrosia</i> differed with latitude. The polyacetylenes were identified to be the most predominant metabolites in <i>Petrosia</i> sponges in temperate regions, while tropical <i>Petrosia</i> species were sources of a greater variety of metabolites, such as meroterpenoids, sterols, polyacetylenes, and alkaloids.