The Physician Orders for Life-Sustaining Treatment (POLST) form is a palliative care tool that contains standardized, actionable medical orders. It is designed to ensure that patient treatment preferences are elicited, communicated, and honored throughout the healthcare system. A systematic review of the literature was conducted to evaluate what is currently known about the POLST program and identify directions for future research. Twenty-three research studies focused on POLST use in the clinical setting were identified. A majority of studies have been conducted all or in part in Oregon, with chart review the most frequently used methodology. Research suggests that POLST is most commonly used in older, white patients who are near the end of life. A nonphysician facilitator usually prepares the POLST form for the physician to review and sign. The orders documented on POLST reflect a wide degree of individualization, with only approximately one-third of patients having orders reflecting the lowest level of treatment in all POLST form sections. Clinicians have generally positive attitudes regarding use of POLST yet report a wide range of challenges. POLST alters treatment in a way that is consistent with orders. However, evidence that POLST reflects patient or surrogate treatment preferences is lacking. Research is needed to evaluate the quality of POLST decisions, explore the experiences of patients and their surrogates, develop decision-support tools, improve clinician education, and assess the effect of POLST on care outcomes through intervention and population-based studies.