In Sub-Saharan Africa, the majority of businesses operate in the form of a small and medium-sized enterprise (SME). SMEs play a significant role in the economic development of many nations. This chapter considers the business environment and entrepreneurship activities in the Sub-Saharan countries of Nigeria, Kenya, Senegal, South Sudan and Tanzania. The review of literature explores issues such as doing business in Africa, size and informality, start-up survival and closure, the determinants of growth and gender issues in African entrepreneurship. Using data from the World Bank Enterprise Surveys, it reflects on the factors affecting investment and productivity in Africa as follows: education of the labour force, access to infrastructure, access to finance, size of firms and other business climate variables. Finally, using data from the aforementioned survey, this chapter draws pertinent conclusions on the business environment of the region in focus.