This paper will deal with four areas of the neurobiology of euphoria. The first section will be a brief discussion of some aspects of the physical chemistry of euphorigens in relation to naturally occurring neurotransmitters and their physiological and behavioral effects. Second, there will be a description of some of the evidence that the brain may have the potential for the synthesis of euphorigens that could play some role in the normal regulation of subjective states in man. The third section will describe some of the barriers to developing euphorigens having long-term efficacy, i.e., the kinds of neurobiological adaptations that the brain can make to agents that alter normal synaptic function. The last section will suggest theoretical and experimental approaches for future research designed to deal with these adaptational processes.