Family has been defined as a social unit related by blood, marriage, and adoption. A network of political, social and economic relationship exists among family members, as well as between family members and the society they live in, and this network has influenced the change in family structure. This paper examines the influence of demographic and socio-economic factors on the changing family structures in Botswana comparatively to other Southern African countries. Data from Population Censuses, Demographic Health Surveys and other related literature are used to examine the influence of: fertility, marriage, education, migration, inheritance patterns, and HIV/AIDS on the family structure. It notes that there is a decline in fertility and marriage patterns in Botswana and other Southern African countries under a review which changes the structure of the family from the traditional (extended family) to the modem (nuclear and single-parent families). The paper argues that the weakening of family structure is also because of inheritance disputes which are influenced by inheritance customary laws that look down upon women empowerment. Furthermore, HIV/AIDS related mortality and morbidity has also wrecked a lot of families. There are many orphans in Southern Africa due to HIV/AIDS.