Background: Ca 2+ played as a ubiquitous secondary messenger involved in plant growth, development, and responses to various environmental stimuli. Calcium-dependent protein kinases (CDPK) were important Ca 2+ sensors, which could directly translate Ca 2+ signals into downstream phosphorylation signals. Considering the importance of CDPKs as Ca 2+ effectors for regulation of plant stress tolerance and few studies on Brachypodium distachyon were available, it was of interest for us to isolate CDPKs from B. distachyon. Results: A systemic analysis of 30 CDPK family genes in B. distachyon was performed. Results showed that all BdCDPK family members contained conserved catalytic Ser/Thr protein kinase domain, autoinhibitory domain, and EF-hand domain, and a variable N-terminal domain, could be divided into four subgroup (I-IV), based upon sequence homology. Most BdCDPKs had four EF-hands, in which EF2 and EF4 revealed high variability and strong divergence from EF-hand in AtCDPKs. Synteny results indicated that large number of syntenic relationship events existed between rice and B. distachyon, implying their high conservation. Expression profiles indicated that most of BdCDPK genes were involved in phytohormones signal transduction pathways and regulated physiological process in responding to multiple environmental stresses. Moreover, the co-expression network implied that BdCDPKs might be both the activator and the repressor involved in WRKY transcription factors or MAPK cascade genes mediated stress response processes, base on their complex regulatory network. Conclusions: BdCDPKs might play multiple function in WRKY or MAPK mediated abiotic stresses response and phytohormone signaling transduction in B. distachyon. Our genomics analysis of BdCDPKs could provide fundamental information for further investigation the functions of CDPKs in integrating Ca 2+ signalling pathways in response to environments stresses in B. distachyon.