Nearly every definition of prayer refers to some type of communication phenomenon, yet most scholars, especially those in the field of communication, have not pursued the study of prayer as communication. This work brings the relational characteristics of communication into contact with the spiritual life of prayer. It employs quantitative and qualitative methodologies to legitimize the study of prayer as a communication phenomenon, create a theoretical model of prayer, provide three empirical tests of the model and apply the model to several different contexts, including health, eastern religions and teaching. The future of communication and prayer research is also considered in terms of theory building, improvements in methodology, and practical applications. This study should be of interest to scholars in the fields of communication, religious studies, psychology and medicine.