This chapter provides an overview of soil microbiota, biological process, and the impacts that pesticides have on the biological component of soil health to serve as a guide for management decisions for food production in current and future agricultural systems in Africa. The objectives of this chapter are to provide background on mechanisms by which pesticides disrupt soil microbiota comprising the microbiome and their biological processes. Pesticides including herbicides, insecticides, fungicides, and nematicides have variable effects on the soil microbiota abundance, diversity, and function that interact with various soil properties. These interactions must be considered in management decisions when desiring to improve soil health and overall biological function and crop productivity. Use of transgenic or genetically modified crops also affects soil microbiota primarily in a detrimental fashion. Smallholder farmers should consider using regenerative agriculture practices to restore soil health and ecosystem service in their production systems.