Terminological distinctions may be quite functional during the development of a field. “Reward” and “punishment” were firstly replaced by “positive” and “negative reinforcement” by B. F. Skinner, in The Behavior of Organisms, which is published in 1938. However, the concepts of “positive reinforcement” and “negative reinforcement” have received their current meaning to indicate increase of probability of behavioral response to reproduce, named positive, or terminate, named negative, a stimulus, respectively, since 1953. The title “Positive and Negative Reinforcement, a Distinction That Is No Longer Necessary; or a Better Way to Talk about Bad Things”, given by Michael(1975), might be regarded as a watershed in behavior-analytic discussions of positive and negative reinforcement. He concluded that distinctions in these terms are confusing and ambiguous. Whether the distinction between positive and negative reinforcement should be preserved was widely discussed by a number of distinguished behavior analysts in more than 40 years. Their comments to this issue published on The Behavior Analyst in 2006. Nevertheless, they didn’t propose a solution that allowed reliable distinction between positive and negative reinforcement. With rapid development of technology and theory in neuroscience in recent years, there was sufficient evidence that indicates involvement of distinctly different neural processes between positive and negative reinforcement. There are two distinct classes, termed the “direct” and the “indirect” pathway projection, neurons at striatum. Plenty of data supported the hypothesis that activity of direct and indirect pathway striatal neurons exerts opposing control over reinforcement and punishment. Activation of direct pathway striatal neurons was reinforcing, whereas activation of indirect pathway was punishing. Of course, positive and negative reinforcement were not only mediated by different pathway projection neurons, but also associated with different synaptic plasticity. Positive reinforcement may be associated with plasticity that enhances synaptic efficacy onto direct pathway neurons, but negative reinforcement may be associated with plasticity that depresses synaptic efficacy onto indirect pathway neurons. Different neural processes between positive and negative reinforcement may be critical to distinguish the concept of positive and negative reinforcement. So, in accordance with the concept of “homeostasis” in physiology, “psychological homeostasis”, which represents the normal basal psychological state, could be used to clarify distinction between positive and negative reinforcement. Marked disturbance in internal or external environment will stimulate the organism and induce bias from psychological homeostasis. In positive bias, the stimulus results in rewarding or enhanced satisfactory salience and therefore positively reinforces the organism to seek for repetition or maintenance of the stimulus, the positive reinforcer. Positive reinforcement can be defined from increase of the probability of behavioral responses seeking for a stimulus inducing positive bias from psychological homeostasis. In negative bias, the stimulus results in punishment or enhanced aversive salience and therefore negatively reinforces the organism to seek for termination of the stimulus, the negative reinforcer. Negative reinforcement can be then defined from increase of the probability of behavioral responses seeking for termination of a stimulus inducing negative bias from psychological homeostasis. Of course, the positive and negative biases from psychological homeostasis can be measured objectively by using behavioral tests, hormone level assays, and so on. This framework may provide insights into understanding the distinction between positive and negative reinforcement, as well as application of those theoretical concepts of positive and negative reinforcement to behavioral interventions in fields like education and therapy.