The extent to which the pressures on the Lake Victoria basin environment impact the health and nutrition of the communities within the region is often not adequately addressed. The burden of diseases and constraints on the health facilities in basin can be traced to the state of the environment, vulnerabilities of communities and livelihood strategies. Predominant health issues in the basin are linked to unsafe water contaminated by microbial and chemical pollutants, poor disposal of human waste, and food insecurity while some of the health problems in the basin are exacerbated by climatic conditions, whose extremes overwhelm the community’s coping capability. This paper documents the health related issues of the basin by relating the environment to the people’s vulnerabilities and ability to cope with the diseases (such as malaria, cholera, bilharziasis, HIV/AIDS and other human and zoonotic ailments) and nutritional imbalances. Proper management of resources of the Lake Victoria basin needs to be urgently undertaken to enhance agricultural productivity and improve nutritional and health potential for the riparian communities. Detection of disease in this region calls for major human and material resources, such as well-equipped health centres and qualified staff. There is a need to integrate more strongly health policies into other development and natural resource utilization programs. There is need to continuously monitor and evaluate health and diseases trends in the basin using a Health and Demographic Surveillance System.