Maize (Zea mays L.) is one of the major crops susceptible to Aspergillus flavus infection and subsequent aflatoxin contamination. Many earlier studies indicated the roles of kernel proteins, especially constitutively expressed proteins, in maize resistance to A. flavus infection and aflatoxin production. In this review, we examined the past and current efforts in identifying maize genes and proteins from kernel, rachis, and silk tissues that may play an important role in resistance to A. flavus infection and aflatoxin contamination, as well as the efforts in determining the importance or involvement of them in maize resistance through biochemical, molecular and genetics studies. Through these studies, we gained a better understanding of host resistance mechanism: resistant lines appear to either express some stress-related and antifungal proteins at higher levels in endosperm, embryo, rachis and silk tissues before A. flavus infection or induce the expression of these proteins much faster compared to susceptible maize lines. In addition, we summarised several recent efforts in enhancing maize resistance to aflatoxin contamination using native genes from maize or heterologous and synthetic genes from other sources as well as from A. flavus. These efforts to either suppress A. flavus growth or aflatoxin production, have all shown some promising preliminary success. For example, maize plants transformed with an α-amylase inhibitor protein from Lablab purpurea showed reduced aflatoxin levels by 56% in kernel screening assays. The antifungal potentials of transgenic maize plants expressing synthetic lytic peptides, such as cecropin-based D4E1 or tachyplesin-based AGM peptides with demonstrated antiflavus activity (IC 50 = 2.5 to 10 μM), are yet to be assayed. Further investigation in these areas may provide a more cost-effective alternative to biocontrol in managing aflatoxin contamination in maize and other susceptible crops.