Aflatoxins (AFs) contamination of cereals is considered one of the greatest food safety concerns worldwide. Occurrence of AFs in maize, wheat, rice and sorghum is highly prevalent with each commodity accounting for more than 10% of world’s AF exposure. Their occurrence as food contaminants is also associated with huge economic losses. AFs are highly stable compounds that cannot be eliminated by regular processing of grains. Hence, prevention of AFs in food and feed is now considered more important than the subsequent interventions to mitigate the deleterious health effects of AFs in human and animals. However, the development of an effective preventive strategy hinges on a clear understanding of the underlying factors influencing AFs production. Therefore, the present review aims to highlight the most significant factors influencing AFs contamination of cereals at pre-and post-harvest stages. This is crucial for effective monitoring of critical control points and optimisation of preventive strategies in food and feed supply chains. Several intrinsic and extrinsic factors have been reported of which nutritional composition, environmental factors (temperature, water activity and relative humidity) and climate change have been identified as primary factors, while pH of the substrate, carbon dioxide (CO2) levels in the gaseous environment, and agronomic and socioeconomic status are the main secondary factors promoting AFs biosynthesis in cereals. Additionally, an overview of global occurrence of AFs in cereals, with their health impacts and various preventive measures have also been highlighted.