Publisher Summary This chapter highlights the major second messenger pathways that are involved in basal ganglia neurotransmission. It reviews that different receptor types co-exist in any given neuron in any particular brain region. These receptors can activate multiple second messenger pathways simultaneously in opposing or synergistic fashion. Thus, cells can integrate information from multiple brain areas. The dynamic integration of various signals is of interest for therapeutic approaches that target disorders of basal ganglia nuclei. It discusses that although many signal transduction pathways seem to involve cyclic adenosine mono-phosphate (AMP) and Ca2+ as second messengers, a surprising level of specificity is achieved for individual pathways. Many factors contribute to specificity including (1) scaffolding and anchoring proteins, (2) modulators of enzymatic activity, (3) protein families with similar properties but different downstream effects, and (4) splice variants of these proteins. These factors make for attractive targets in drug discovery pursuits with the goal to treat disorders ranging from neuro-psychiatric disorders to cancer. The chapter concludes that in the context of the basal ganglia, neurologic disorders such as Parkinson's disease or Huntington's disease, and psychiatric disorders such as mood disorders or schizophrenia, may soon be treated with drugs that specifically target defined signaling pathways in disease-causing subsets of neurons.