Africa has the unenviable challenge of dealing with a double burden of disease: infectious diseases (IDs) such as HIV/AIDS and tuberculosis are high while non-communicable diseases (NCDs) are rapidly rising in the region. Populations with increased susceptibility to both include migrants. This review highlights the susceptibility of rural-to-urban migrants in Sub-Saharan Africa to the IDs of HIV/AIDS and tuberculosis, and to NCDs, particularly cardiovascular diseases. The disruption that occurs with migration is often accompanied by unhealthy exposures and environments. These include partaking in risky sexual practices and a subsequent greater risk for HIV infection in migrants than the general populations which contributes to the spread of the disease. Migrants frequently work and live in conditions that are poorly ventilated and overcrowded with suboptimal sanitation which increases their risk for tuberculosis. Considering that migrants have an increased risk of acquiring both HIV/AIDS and tuberculosis, and in view of the interaction between these diseases, they are likely to be at high risk for co-infection. They are also likely to facilitate the geographical spread of these infections and serve as conduits of disease dissemination to rural areas. Changes in lifestyle behaviours that accompany migration and urbanisation are exemplified primarily by shifts in physical activity and dietary patterns which promote the development of obesity, diabetes, hypertension and cardiovascular diseases. Urban living and employment is generally less physically exerting than rural routines; when migrants relocate from their rural residence they adapt to their new environment by significantly reducing their physical activity levels. Also, nutritional patterns among migrants in urban centres change rapidly with a shift to diets higher in fat, sugar and salt. Consequently, increases in weight, blood pressure and glucose levels have been reported within a year of migration. Interactions between IDs and NCDs are common; considering that migrants have an increased susceptibility to IDs and demonstrate a rapid rise in their risk for NCDs, the concurrent prevalence of both is likely in this population. There is a need for a combined strategy to combat IDs and NCDs with screening and treatment programmes geared towards this high risk group.