Calcineurin B-like interacting protein kinase CIPK (CBL interacting protein kinases) is one of important protein kinases in the plant calcium signal pathway in response to abiotic stresses. Based on the sequence information of the CIPK family genes in Arabidopsis and rice, the members of the maize CIPK gene family were identified from the maize reference genome B73. The evolution relationship, structure variation, transcriptional profile, and transcriptional re-programing under drought stress treatments of CIPK family genes were analyzed. Forth-four maize CIPK family genes were identified and classified into five sub-families, each of which represented different characteristics on exon-intron and UTR structure. Based on the analysis of transcriptional profiles under drought stress condition, five candidate genes (ZmCIPK3, ZmCIPK7, ZmCIPK44, ZmCIPK25 and ZmCIPK28) involving into drought tolerance were identified. Furthermore, by over-expressing the ZmCIPK3 gene in Arabidopsis thaliana, under drought stress conditions the survival rate of ZmCIPK3-transgenic lines was significantly higher than that of the wild type, suggesting that ZmCIPK3 might increase the drought resistance. The activities of peroxidase (POD) and superoxide dismutase (SOD) in transgenic lines were significantly higher than those of the wild type, while the contents of malondialdehyde (MDA) and proline (Pro) were significantly lower than those of wild type. This study identified the members of the maize CIPK gene family at the genome-wide level and their transcriptional profile upon drought stress treatments, and confirmed ZmCIPK3 as a candidate gene conferring drought tolerance.