Importance: The number of patients living with end-stage heart failure is steadily growing, and ambulatory intravenous inotropic support is increasingly offered as a palliative therapy. However, the optimal ways to initiate, manage, and discuss the risks and benefits of palliative inotropes in the current era of heart failure care are unclear. Observations: The initiation of palliative inotropes requires an understanding of clinical, psychosocial, and economic factors, as well as the changing risk-to-benefit calculus. While earlier studies suggested that outpatient inotrope therapy provided symptomatic benefit at the expense of reduced survival, recent data suggest that the survival of patients receiving chronic inotropes may be improving over time, perhaps owing to the use of implantable cardioverter defibrillators, concurrent guideline-directed medical therapy, or lower doses of inotropes. The use of heart failure therapies, such as beta-blockade, among patients receiving palliative inotropes is controversial but may be appropriate in select situations. Conclusions and Relevance: The role of palliative inotropes is changing in tandem with advances in chronic heart failure care. However, there remains a profound lack of data and guidance on the effect of palliative inotropes on quality of life and mortality and little consensus on how this therapy can be optimally used in contemporary practice. This review provides a framework for the prescription and management of palliative inotropes, including a discussion of potential risks and benefits and a roadmap for how to initiate, maintain, and wean them.