Prognostication is the science by which clinicians estimate a patient's expected outcome. A robust literature shows that many patients with advanced cancer have inaccurate perceptions of their prognosis, thus raising questions about whether patients are truly making informed decisions. Clinicians' ability to communicate prognostic information is further complicated today by the availability of novel, efficacious immunotherapies and genome-guided treatments. Currently, clinicians lack tools to predict which patients with advanced disease will achieve an exceptional response to these new therapies. This increased prognostic uncertainty on the part of clinicians further complicates prognostic communication with patients. Evidence also suggests that many oncologists avoid or rarely engage in prognosis-related communication and/or lack skills in this area. Although communication skills training interventions can have a positive impact on complex communication skills for some clinicians, there is no one-size-fits-all approach to improving patient-clinician communication about prognosis. Yet improving patient understanding of prognosis is critical, because patient understanding of prognosis is linked with end-of-life care outcomes. Solutions to this problem will likely require a combination of interventions beyond communication skills training programs, including enhanced use of other cancer clinicians, such as oncology nurses and social workers, increased use of palliative care specialists, and organizational support to facilitate advance care planning.