The second messenger molecule cyclic di-AMP (c-di-AMP) is formed by many bacteria and archaea. In many species that produce c-di-AMP, this second messenger is essential for viability on rich medium. Recent research has demonstrated that c-di-AMP binds to a large number of proteins and riboswitches, which are often involved in potassium and osmotic homeostasis. c-di-AMP becomes dispensable if the bacteria are cultivated on minimal media with low concentrations of osmotically active compounds. Thus, the essentiality of c-di-AMP does not result from an interaction with a single essential target but rather from the multilevel control of complex homeostatic processes. This review summarizes current knowledge on the homeostasis of c-di-AMP and its function(s) in the control of cellular processes.