This paper examines the conditions that describe when it is appropriate to conduct research that enrolls a subject near the end-of-life who cannot provide an informed consent. Specifically, it describes conditions that justify when it is acceptable to expose a person to the risks, burdens or discomforts of an intervention that is not intended to benefit that person but to produce generalizable knowledge that will benefit other people. These conditions are: (1) acceptable research risks, (2) proxy decision making, (3) subject assent and dissent, and (4) subject advance consent.