The best practice of oncology relies heavily on a mentally and physically healthy oncology clinician workforce. Historically, the mental health of physicians and clinicians has largely been ignored, perhaps in the spirit of a collective collusion to maintain the illusion of Oslerian equanimity. With exceedingly high and unacceptable rates of burnout and suicide in the practice of medicine and oncology in particular, a tacit disavowal of the problem is no longer acceptable. The practice of oncology presents several unique work-related issues that challenge the mental health of its clinicians and contribute to burnout, depression, and suicide. Oncologists work with patients at or nearing the end of life and face administrative and insurance hurdles to obtain needed anticancer medications, heavy workloads, paperwork and electronic medical record demands, and keeping up with expanding pertinent oncologic knowledge for practice and public relations issues. Although oncologists exhibit higher rates of depression with longer work hours than many other internal medicine colleagues, they have higher job satisfaction ratings. This article will (1) review the mental health of professionals in oncology, (2) explore similarities and differences between depression and burnout, (3) describe the unique nature of the oncology work environment, (4) examine suicide and its implications for oncology, and (5) review the evidence for interventions to prevent burnout and suicide. Although individual and system-level strategic approaches to the problem of burnout and its consequences are effective, combinatorial approaches offer the most hope for affecting the most long-lasting change and lessening burnout, depression, and suicide in oncology.