Being universal second messengers in bacteria, cyclic dinucleotides (CDN) such as cyclic dimeric guanosine 3’,5’-monophosphate (c-di-GMP) and cyclic dimeric adenosine 3’,5’-monophosphate (c-di-AMP) are important multi-functional compounds that regulate a diverse range of processes in bacteria. After the discovery of c-di-GMP as a trigger for an innate immune response in mammalian host cells, CDN have been of topical interest as vaccine adjuvants and immunotherapeutics. This review highlights the innovative discovery backed up by the achievement of efficient CDN synthesis and the CDN analogues for the future therapeutics.