The cinnoline nucleus is a bicyclic ring and is an isosteric precursor to quinolone or isoquinoline. Cinnoline analogs are aromatic heterocyclic compounds having diverse therapeutic activities, such as antimicrobial, analgesic, anti-inflammatory, anti-tuberculosis, antimalarial, anticonvulsant, antioxidant, anticancer, antihypertensive, anti-anxiety, and other activities. This heterocyclic nucleus is attracting a lot of attention in medicinal chemistry and is used as a structural subunit in various compounds with attractive medicinal and chemical properties. In this review, we focus on the biological activities of cinnoline analogs with various substitutions.