Clinical research is the cornerstone of the progress recorded in psychiatry in the last six decades, or of what is called the psychopharmacological revolution. Regardless of the stage of clinical research, there are sensitive ethical and legal aspects that may appear during this process, and such challenges have to be acknowledged in order to preserve its scientific value, integrity, and centered-on-the-patient-wellbeing core principles. Also, adequate strategies focused on preventing the risk of ethical misconduct and litigation have to be found to avoid a loss of trust in the results of clinical research, to protect vulnerable populations from abuse, and to ensure a legally stable environment for investigators. In order to explore these practical problems, a narrative review was performed through a search in PubMed and Google Scholar databases. The main ethical risks detected in clinical research were related to errors in the methodology of obtaining informed consent, monitoring the participant's safety during the clinical trial, and falsifying collected data. Several famous cases of ethical misconduct were found and analyzed, and methods to decrease the risk of the re-appearance of such problems have been listed. In conclusion, this review is an invitation to explore the complexity of the methodology of clinical research and its ethical and legal risks, as well as to find new ways to mitigate the possibility of such risks related to the research process.