Pyrazine belongs to the 1, 4-diazines family, which is a significant class of heterocyclic compounds. Various pyrazine derivatives have been produced and successfully confirmed as medicines with various pharmacological activities like anti-inflammatory, antitubercular, anticancer, antibacterial, and neurological activity, with some of them becoming clinically utilized pharmaceuticals globally. This review includes a survey on pyrazine derivatives possessing different pharmacological activities. The class of pyrazine-based potential medications has grown rapidly in terms of both the absolute quantity of studied compounds and the range of various biological activities. Additionally, there is a lot of potential for this scaffold, which medicinal chemists ought to investigate for the creation of novel potential drug candidates.