Artificially increasing dopamine transmission is the common mechanism by which substances with addictive potential lead to addiction. A key area of research in neurobiology is the role of dopamine. Significant advancements have been made in uncovering the intracellular signaling pathways that mediate both dopamine's immediate effects and its long-term influence on brain function. Recent discoveries have also highlighted specific molecules that could serve as potential therapeutic targets for neurological and psychiatric disorders. While understanding several important caveats, we believe dopamine acts as a master regulator of brain circuitry across major chromosomes mapping the mental health genome. This view may have important clinical relevance, emphasizing the critical role of dopaminergic activity across the genome. Importantly, we are cognizant that dopamine does not work in insolation, and its finite actions are due to a highly interactive network (known as the brain reward cascade), involving at least seven other major neurotransmitters.