Natural products possess immense potential as a source of antiviral drugs. Numerous antiviral natural products have been discovered, many of which are promising antiviral drug candidates currently undergoing various stages of clinical and preclinical investigation. However, the status of antiviral natural products isolated from African traditional medicinal plants remains largely unexplored. This chapter therefore provides a comprehensive review of the chemistry and antiviral potential of various classes of natural products as well as extracts derived from African medicinal plants and discusses their future prospects. A total of 81 antiviral terpenoids, alkaloids, and phenolics, along with 2 anti-HIV proteins isolated from African medicinal plants, are described. Notably, 53% of these compounds are novel and potent antivirals. In addition, there are 101 African medicinal plants belonging to 42 families and 79 genera with extracts and fractions active against various pathogenic viruses. Nevertheless, these natural products are at early stages of antiviral drug development; hence, further studies and approaches needed to enhance their potency and selectivity and to translate them into clinical candidates are discussed. Furthermore, the discovery of novel antivirals from untapped African traditional plant resources using different innovative techniques is briefly highlighted.