Pests are a threat to agricultural productivity. The current pest management approaches with pesticides are riddled with a plethora of challenges, such as non-selective toxicity, pest resistance to pesticides and bioaccumulation in tissues. The pest challenge requires the search for eco-friendly and safer alternatives from natural sources. This chapter considers plant secondary metabolites and other natural sources as actual or potential pesticides. We discuss the categories of pesticides and pests of economic importance in Africa, with an emphasis on medicinal plants with promising bioactivities. We use a holistic approach to pest management while promoting the traditional use of plant diversity for the benefit of agriculture and the environment. This chapter further highlights the benefits that can be derived from bridging farmer pest management knowledge and scientific techniques. The most promising secondary metabolites from plants were saponins, terpenoids, anthocyanins, tannins, leucoanthocyanidins and emodins. Tannins through oxidation inhibit protein digestion, hinder insect growth and cause insect death. Alkaloids are neurotoxic and have anti-repellent and antifeedant effects, while terpenoids interfere with metamorphosis and other physiological processes in insects. The most promising secondary metabolites can be scientifically exploited and their use enhanced through identification, extraction, isolation, characterization, formulation and application in comprehensive pest management. The biopesticides with the most promising activity work through various mechanisms that deter certain pests’ activities for their growth and survival. However, most of the pesticides extend their activity by inhibiting octopamine and tyramine receptors, interfering with the receptors for the juvenile hormone and inhibiting the action of gamma-aminobutyric acid. Some of the opportunities for using secondary metabolites in pest control include restrictions by most governments on production of chemical pesticides and promotion of green agricultural practices. Despite these prospects, some challenges in using secondary metabolites in pest control are eminent. These include high costs of production, inconsistent performance, limited shelf life, lack of large-scale production facilities, lengthy regulation process and limited research to establish active ingredients of the plants used in pest control. This chapter is a valuable resource in exploring approaches to pest management while promoting the utilization of indigenous knowledge and biodiversity. In conclusion, an increase in agricultural productivity can be achieved if the challenge of pests is addressed using eco-friendly approaches, one of which is the use of biopesticides. This calls for further research to incorporate indigenous traditional knowledge in the development of safe and effective biopesticides through identification and separation of active ingredients.