The midbrain dopamine system, crucial for controlling multiple physiological functions, is integrated through diverse inputs and involves the ventral tegmental area (VTA). Dopamine, a neurotransmitter, works with other neurotransmitters and neuropeptides to maintain synaptic balance. The VTA, a key relay nucleus, modulates homeostatic plasticity in the dopamine system. This review focuses on the cell types, neurotransmitters, neuropeptides, ion channels, receptors, and neural circuits of the VTA dopamine system, aiming to provide new insights into its formation and function. The development of the dopamine system is critical for understanding neuropsychiatric and neurological disorders. Dopamine neurons originate from the neural tube floor plate and undergo complex developmental processes. Transcription factors like Lmx1b and Sox6 play guiding roles in their differentiation. Invertebrates also exhibit dopamine-related behaviors, with specific receptors and signaling pathways. The VTA contains various cell types, including dopaminergic, glutamatergic, and GABAergic neurons, each with distinct ion channels and receptors. HCN channels, KCNQ channels, dopamine receptors, serotonin receptors, and adrenergic receptors are essential for processing information and modulating VTA activities. Neuropeptides like CRF, neurotensin, orexin, dynorphin, oxytocin, and cholecystokinin also influence VTA functions. The VTA projects to the nucleus accumbens (NAc), prefrontal cortex (PFC), and central amygdala (CeA), with reciprocal connections. These projections are involved in reward processing, decision-making, and stress responses. The VTA also receives inputs from the lateral habenula (LHb) and rostral medial tegmental nucleus (RMTg), which modulate VTA activities. Dysfunction of the dopamine system leads to conditions such as Parkinson’s disease, Huntington’s disease, schizophrenia, and major depression. The VTA's role in these disorders is multifaceted, involving both degeneration and hyper-regeneration of dopamine neurons. In conclusion, the VTA dopamine system is a complex network that integrates multiple neurotransmitters and neuropeptides to regulate various behaviors and functions. Further research is needed to understand how these components coordinate to maintain homeostatic plasticity and to develop effective treatments for dopamine-related disorders.The midbrain dopamine system, crucial for controlling multiple physiological functions, is integrated through diverse inputs and involves the ventral tegmental area (VTA). Dopamine, a neurotransmitter, works with other neurotransmitters and neuropeptides to maintain synaptic balance. The VTA, a key relay nucleus, modulates homeostatic plasticity in the dopamine system. This review focuses on the cell types, neurotransmitters, neuropeptides, ion channels, receptors, and neural circuits of the VTA dopamine system, aiming to provide new insights into its formation and function. The development of the dopamine system is critical for understanding neuropsychiatric and neurological disorders. Dopamine neurons originate from the neural tube floor plate and undergo complex developmental processes. Transcription factors like Lmx1b and Sox6 play guiding roles in their differentiation. Invertebrates also exhibit dopamine-related behaviors, with specific receptors and signaling pathways. The VTA contains various cell types, including dopaminergic, glutamatergic, and GABAergic neurons, each with distinct ion channels and receptors. HCN channels, KCNQ channels, dopamine receptors, serotonin receptors, and adrenergic receptors are essential for processing information and modulating VTA activities. Neuropeptides like CRF, neurotensin, orexin, dynorphin, oxytocin, and cholecystokinin also influence VTA functions. The VTA projects to the nucleus accumbens (NAc), prefrontal cortex (PFC), and central amygdala (CeA), with reciprocal connections. These projections are involved in reward processing, decision-making, and stress responses. The VTA also receives inputs from the lateral habenula (LHb) and rostral medial tegmental nucleus (RMTg), which modulate VTA activities. Dysfunction of the dopamine system leads to conditions such as Parkinson’s disease, Huntington’s disease, schizophrenia, and major depression. The VTA's role in these disorders is multifaceted, involving both degeneration and hyper-regeneration of dopamine neurons. In conclusion, the VTA dopamine system is a complex network that integrates multiple neurotransmitters and neuropeptides to regulate various behaviors and functions. Further research is needed to understand how these components coordinate to maintain homeostatic plasticity and to develop effective treatments for dopamine-related disorders.