Although Peplau’s theory of interpersonal relations had been published in 1952 and widely integrated within nursing practice thereafter, it had not been empirically tested through research. What was known is that (a) factors within the orientation phase of the therapeutic relationship had the most predictive outcomes in psychotherapy among individuals with chronic mental health challenges, (b) difficulty in establishing the therapeutic relationship was related to poorer outcomes in treatment, and (c) the first six months of the therapeutic relationship was a critical time period to develop a working alliance. This chapter follows the testing of Peplau’s theory among 124 nurse–client dyads over six months’ time. The concepts of the theory were shown to predict which of the nurse–client dyads were able to establish working relationships more quickly as well as the quality of these relationships.