Cyclic dinucleotides of bacterial and host origin have emerged as second messengers with fundamental biological roles in bacterial physiology and host immunity. This new field faces a number of broad questions that we aim to answer. (i) What are the molecular mechanisms of c-di-AMP signal transduction within bacteria? (ii) What are the contributions of cyclic dinucleotide production to bacterial virulence? (iii) How does cyclic dinucleotide signal transduction in the host alter infection outcome? We utilize multidisciplinary approaches in chemistry, biochemistry, bacterial genetics, tissue culture and in vivo infection models to elucidate the mechanisms by which these ubiquitous second messengers shape bacterial physiology and host-microbe interactions.