Maize is the most important staple food crop for over 300 million people in sub-Saharan Africa but poor management practices and problems related to climate and soil quality mean that yields regularly fall below what is needed to feed the population. This chapter describes the effect of poor soil fertility, drought and weeds (especially Striga hermonthica) on maize yields. It then puts forward evidence-based strategies for mitigating these constraints, including nutrient management through the use of fertilizers on maize yields and approaches to weed management such as genetic engineering of tolerant and resistant maize varieties. Finally, the chapter examines ways of dealing with the challenge of drought, including improved irrigation and genetic engineering of drought-resistant maize varieties.