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Interpersonal psychotherapy (IPT) is an evidence-based, time-limited, and affect-focused psychotherapy that was developed 50 years ago for major depression and has now been expanded to treat other mood and nonmood disorders, including in patients with cancer, in a variety of settings worldwide. Core principles of IPT include that depression often occurs in the context of major life events and that it is a medical illness that is not the patient’s fault. This chapter will first describe the background and development of IPT, then discuss the research on efficacy of IPT in patients with cancer and other medical illnesses as well as limitations of the existing data. It will outline principles of IPT and illustrate the major phases of treatment with basic techniques through use of the case vignette of “Ms. A,” a patient with breast cancer and depression. Lastly, it will review relevant adaptations of IPT including interpersonal counseling (IPC), an abbreviated version of IPT for less psychotherapeutically trained clinicians that has been studied in psycho-oncology patients. Though data on psychotherapy in patients with cancer remain limited, IPT appears to be a practical and promising option that warrants current use and further study.