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Pyrido[2,3‐d]pyrimidine, a fused hetero‐bicyclic nucleus containing pyridine and pyrimidine rings has attained the momentary attention in the sphere of multicomponent synthetic protocol and medicinal chemist. Pyrido[2,3‐d]pyrimidine derived drugs have manifested diverse pharmacological activities, particularly, anti‐inflammatory, cytotoxic, antimicrobial, phosphodiesterase inhibitors and cytokine inhibitors etc. The present review illustrates various modern synthetic strategies adopted, the structure–activity relationship (SAR) aspects and discloses the extensive crucial biological properties (anticancer, anti‐infectious, anti‐diabetics and CNS agents) of pyrido[2,3‐d]pyrimidines.