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This chapter discusses the basic ethical principles and practices for human experimentation. It touches on the related subject of regulatory and legal issues in neurological research. Disorders of the central nervous system (CNS) present a number of challenges for specifying core principles and practices of research ethics. In CNS research, the tensions between regulation and ethics are greatest around the use of placebo controls. Phase 1 trials of new CNS interventions, as with all interventions, generally present a high degree of risk and uncertainty. Many trials involving neurological disorders show evidence of placebo responses. Many CNS drug trials involve brain imaging, in one report, brain abnormalities, like malignancies or vascular malformations, were detected in as many as 18% of healthy volunteers. Issues of justice arise with particular frequency whenever CNS trials involve placebos. Researchers should also attend to various non-verbal or affective elements of communication that shape public expectations.