cAMP is an important second messenger in both eukaryotic and prokaryotic organisms. Several bacterial pathogens have developed mechanisms to subvert eukaryotic cAMP signaling by injecting protein toxins that are themselves adenylate cyclases or by introducing toxins that modify host adenylate cyclases to an overexpression state. Curiously, Mycobacterium tuberculosis CDC1551 genome contains seventeen adenylate cyclase homologues suggesting that cAMP signaling is both relevant and complex in biology of M. tuberculosis. The present article provides an overview of the role of cAMP as a second messenger, discusses bacterial cAMP subversion mechanisms, and reviews the evidence currently available on cAMP-based signaling in M. tuberculosis.