Conducting studies at the end of life is often challenging for researchers due to the sensitive nature of the research, the vulnerability of the participants and the inherent methodological complexities. Methodological challenges include identifying and gaining access to eligible research participants, estimating the duration of patient survival time in the study, minimizing the potential burden of data collection, and attending to issues of consent and confidentiality. In this paper, the authors identify challenges when conducting end-of-life research and draw from collective research experiences to describe strategies to achieve success.