The immense amount of research on benzodiazepines resulted in the synthesis of heterocycle-fused diazepine derivatives with potential pharmacological activity. Pyridoazepines are recognized to be active in the central nervous system and have a comparable activity to the well-known benzodiazepines. This makes the synthesis and the study of pyridodiazepines an important research topic. This review comprises of the synthesis and activity of pyridodiazepines, pyridooxazepines and pyridothiazepines. Although these structures have a great similarity with benzodiazepines, much less work has been published on their synthesis or derivatization. Therefore, there is a need to further develop these classes of underexplored scaffolds, in search for new chemistry, new methodology and hence new biological features.