Huntington disease (HD) is an inherited neurodegenerative disorder caused by an expansion of the CAG repeat region in the first exon of the huntingtin gene. Neurodegeneration, which begins in the striatum and then spreads to other brain areas, is preceded by dysfunction in multiple aspects of neurotransmission across a variety of brain areas. This review will provide an overview of the neurochemical mediators and modulators of synaptic transmission that are disrupted in HD. This includes classical neurotransmitters like glutamate and gamma‐aminobutyric acid, modulators such as dopamine, adenosine and endocannabinoids, and molecules like brain‐derived neurotrophic factor which affect neurotransmission in a more indirect manner. Alterations in the functioning of these signaling pathways can occur across multiple brain regions such as striatum, cortex and hippocampus, and affect transmission and plasticity at the synapses within these regions, which may ultimately change behaviour and contribute to the pathophysiology of HD. The current state of knowledge in this area has already yielded useful information about the causes of synaptic dysfunction and selective cell death. A full understanding of the mechanisms and consequences of disruptions in synaptic function and plasticity will lend insight into the development of the symptoms of HD, and potential drug targets for ameliorating them. Early Huntington disease is characterized by involuntary motor symptoms, especially chorea, due to dominance of direct pathway Striatal Projection Neurons (SPN) which facilitate movement. Initially, deficits in endocannabinoid and BDNF signaling, increased dopamine and GABA contribute to impair some forms of synaptic plasticity in indirect pathway SPNs, as well as their vulnerability to degeneration before other cell types. In this paper we summarize mutant huntington (mHtt)‐induced changes in neurotransmission in the striatum and cortex. DA, dopamine; dSPN, direct pathway SPN; eCB, endocannabinoid; iSPN, indirect pathway SPN.