Abstract: PKCθ, which is expressed predominantly in T cells, it is required for the activation of T cells. PKCθ also positively and negatively regulate effector and regulatory T cells' differentiation and function, respectively. These attributes of PKCθ make it an attractive target for novel selective immunosuppressant. To date, there has been reported several chemical types of small-molecule PKCθ inhibitors. Herein, these synthetic or natural PKCθ inhibitors or those in clinical trial phase are reviewed, and discussed the problems needed to be solved in the development of PKCθ inhibitors. In the coming years, PKCθ inhibitors may be served as new generation of immunosuppressant and benefit patients with immunological disease.