This review examines the biosafety systems of selected countries in the Eastern and Central Africa. The biosafety systems are meant to safeguard human health, animal health and the environment against any possible risks posed by development and application of modern biotechnology. Though the focus is in the Eastern and Central African region, the study gives an overview of worldwide biosafety frameworks as guided by the Cartagena protocol on biosafety. The Eastern and Central African countries covered in this study are Tanzania, Kenya, Uganda, Rwanda, Burundi, Ethiopia and the Democratic Republic of Congo (DRC). An attempt is made to assess the current status on the countries’ compliance to biosafety international conventions, institutional arrangements and regulatory regimes. A critical look is given to the existing biosafety frameworks, pinpointing their weaknesses and giving suggestions on what could be done to address the shortfalls. The study shows that Kenya is leading the group by having all the requirements in place, followed by Uganda. Tanzania has cleared the legal frameworks hurdles, but it is rather slow in processing applications of genetically modified organisms (GMOs) for containment and confined trials. Ethiopia, Rwanda, Burundi and DRC are still in the process of formulating their biosafety laws. The challenges facing the operationalization of the biosafety systems are financial constraints, insufficient trained human resources, poor facilities, low awareness and insufficient political will by some governments. It is argued that while biosafety frameworks stand to safeguard safe application of modern biotechnology, they should not have too stringent regulations, lest they impede the development of modern biotechnology in the Eastern and Central African region.