A review of the available data from macrobotanical analyses conducted on prehistoric archaeological sites found in coastal southern California indicates the ubiquitous nature of carbonized Marah macrocarpus (Greene) Greene (wild cucumber) seed coat fragments. Their recovery from cultural deposits in carbonized form indicates prehistoric use; however, all parts of the plant are toxic, and plants that typically function in medicinal or ritualistic roles are rarely recovered as part of the macrobotanical assemblage. In an attempt to shed some light on the possible prehistoric uses of wild cucumber by the native peoples of coastal southern California, this paper examines the current distribution of Marah, the archaeological occurrence of M. macrocarpus, as well as pertinent biochemical and morphological characteristics of the plant, particularly the seed. Finally, ethnobotanical accounts of the use of Marah by the native peoples of the Pacific west are discussed in light of current research on the physical properties and biological activities of various compounds found in Marah. This information is offered as a guide for future archaeological investigations of the possible uses of the taxon by the prehistoric Indians of coastal southern California and elsewhere.