Substance addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite harmful consequences. Non-substance addiction has recently been defined as compulsive engagement in non-drug-related rewarding activities (e.g., gambling) despite negative consequences. Although differences exist with respect to addictive objects, substances, and non-substance, addictions may share overlapping biological, epidemiological, clinical, and genetic features. Studies have shown that brain circuitry, as well as dopamine, serotonin, opioid, glutamate, and norepinephrine systems in the brain, is involved in both substance and non-substance addictions, but their specific contributions are debated. Here, we review the currently known overlapping and distinct neurotransmitter systems associated with these two types of addictions.