Many studies have been carried out to find synthetic pathways to nicotinonitriles (3-cyanopyridines) and their analogs, which has resulted in a substantial amount of knowledge on their biological, therapeutic, and medical characteristics. Some of nicotinonitrile derivatives have emerged as marketed drugs such as bosutinib, milrinone, neratinib, and olprinone. In this review, we discuss the recently synthesized nicotinonitrile-based hybrids that possess important biological activity and will be useful for drug discovery and development.