Research involving vulnerable population of mentally impaired persons is raising considerable controversies from its very beginnings. These controversies are created around everlasting tensions between two positive duties: the duty to protect vulnerable subjects, and the duty not to deny them potential benefits. Most of the contemporary ethical guidelines and regulations, including most recent revision of the Declaration of Helsinki, permit these researches under certain ethical conditions. The notion of informed consent as a cornerstone of bioethics emerges as essential requisite of moral research. We are presenting some key concepts and safeguards regarding informed consent that researcher needs to be aware off when conducting a research involving mentally impaired persons. Theoretical and practical challenges that are arising from these safeguards are discussed with an overview of most recent scientific data. Lastly, we briefly address the most important legal standings that will be introduced in 2015, by new Croatian Law on the Protection of Persons with Mental Disorders.