The aim of the study was to explore the views of tuberculosis (TB) physicians on treatment of latent TB infection (LTBI), focusing on decision making and communication in clinical practice. 20 Australian TB physicians participated in a semistructured interview in person or over the telephone. Interviews were recorded, transcribed and analysed thematically. The study identified challenges that physicians face when discussing treatment for LTBI with patients. These included difficulties explaining the concept of latency (in particular to patients from culturally and linguistically diverse backgrounds) and providing guidance to patients while still framing treatment decisions as a choice. Tailored estimates of the risk of developing TB and the risk of developing an adverse effect from LTBI treatment were considered the most important information for decision making and discussion with patients. Physicians acknowledged that there is a significant amount of unwarranted treatment variation, which they attributed to the lack of evidence about the risk-benefit balance of LTBI treatment in certain scenarios and guidelines that refer to the need for case-by-case decision making in many instances. In order to successfully implement LTBI treatment at a clinical level, consideration should be given to research on how to best address communication challenges arising in clinical encounters.