The Menispermaceae comprises some 75 genera and 520 species and is widespread in tropical and subtropical countries. Approximately 25 genera with 101 species are found in Africa. The southern African Menispermaceae comprises 7 genera and 13 species, of which one genus (Antizoma) and one species (Cissampelos capensis) are endemic. Field and herbarium surveys succeeded in expanding the knowledge on the geographical distribution of the South African species and a taxonomic synopsis is presented. A key to the 13 species was developed in which they can clearly be distinguished according to leaf morphology. The generic status of Antizoma was always somewhat problematic. Based on morphological features and growth habit, the two species of Antizoma seem to be adaptations to xerophytic conditions and are hardly different to Cissampelos capensis. Cladistic analysis of morphological and alkaloid data indicated strongly that Antizoma is nested within the genus Cissampelos. It is therefore proposed that the genus Antizoma be subsumed within Cissampelos. The family Menispermaceae is highly specialized in its rich diversification of bisbenzylisoquinoline alkaloids. Because of this richness the family is used worldwide in traditional medicines to treat a wide variety of ailments. From the 13 species Cissampelos capensis [(dawidjies (wortel)] is the best known and most used medicinal plant especially by the Khoisan and other rural people in the western region of South Africa. An ethnobotanical survey had confirmed the known medicinal uses and added several additional anecdotes for this species. Very few medicinal uses were hitherto recorded for the other 12 species and this study now adds several new records. The ethnobotanical survey also indicated that Cissampelos is the most widely and frequently used genus in this family in South Africa, Africa and the rest of the World. Seventeen alkaloids from seven species were isolated, using column chromatography, and identified with nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). No new alkaloids were identified during this study. Chemotaxonomic comparisons between species, provenances (different localities) and different plant parts of the same species, were done by using analytical crude alkaloid extracts. Alkaloids in these samples were identified withanalytical thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) using pure reference standards obtained from own isolations. Significant differences in the presence and concentration of alkaloids in different plant parts and between populations indicated that alkaloids can be a useful chemotaxonomic tool, but an appropriate sampling strategy is a pre-requisite. Clear alkaloid patterns emerged for the seven species studied. The occurrence of alkaloids in plants was affected by locality as was confirmed by the difference in alkaloid patterns between coastal and inland forms of Cissampelos capensis. Antimalaria and anticancer screening were done on all 13 species and the significant positive results obtained support the ethnobotanical knowledge that some Menispermaceae species are used as antimalarial and anticancer medicines. The biological activities of some of the identified alkaloids also support the rationale behind the medicinal uses of the 13 South African species. Most of them are used as bitter tonics (“amara”) or stimulants. This study therefore succeeded in contributing to the knowledge about the ethnobotany, chemotaxonomy and biological activities of the South African members of this important and interesting family.Prof. B.E. van Wy