Research in palliative care is crucial for continuously improving the evidence base of palliative care. However, palliative care research is also confronted with (both real and perceived) ethical challenges. This chapter explores the ethical challenges with a particular focus on those challenges that are particular to palliative care research. In a first part, focus lies on the important concept of (research) vulnerability as research in palliative care is often argued to include participants from a vulnerable population. It will be argued that—although important—using vulnerability as a concept comes with certain important drawbacks. In a second part, this chapter explores several ethical requirements that research should uphold in order to be ethically justified. These are (1) respect for research participants; (2) the need for independent review; (3) the requirement of social and/or scientific value; (4) issues related to informed consent; (5) challenges regarding scientific validity; (6) favorable risk-benefit ratio; and (7) fair participant selection. Each of these requirements will be discussed focusing on their relevance for palliative care research in particular. In short, doing palliative care research in the most ethical way will require continuous ethical reflection on behalf of everyone involved. This chapter aims to supply everyone with elements that can inspire and guide such a reflection.