In this report, we describe the case of an 81-year-old male with reactivation tuberculosis following local radiation therapy for prostate cancer. The patient was asymptomatic except for an unintentional 20-pound weight loss and was incidentally found to have a pulmonary infiltrate in the right upper lobe on imaging for shoulder pain. The medical history was not able for recently treated prostate cancer. After further investigation, the patient was determined to have Mycobacterium tuberculosis infection. It is important to have a high level of suspicion for reactivation tuberculosis in patients with a pulmonary infiltrate following radiation therapy due to the impact of radiation on the host's immune system. We will review the literature on reactivation tuberculosis following radiation therapy and explore the mechanism of immunosuppression in this process. To our knowledge, this is the first reported case of tuberculosis reactivation following local radiation therapy for prostate cancer.