Background: Research with adults who cannot give informed consent has important social value. However, enrolling adults who cannot consent in research raises significant ethical concerns. Methods: To evaluate how researchers in low and middle-income countries (LMICs) can assess individuals' decisional capacity, and the conditions under which it is appropriate, and the conditions under which it is not appropriate to include individuals who lack decisional capacity. Results: In LMICs, where resources may be limited, implementing protections for adults with decisional incapacity can be especially challenging. Recognition of the ethical concerns, and awareness of the circumstances and available resources, offers the means to protect these vulnerable participants. Conclusions: Researchers in low and middle-income countries should be aware of steps they can take to ensure appropriate protections for subjects with decisional impairments while conducting clinical trials on methods to improve their clinical care.