This aim of this chapter is to review literature on the excitability and function of dopamine neurons that originate in the midbrain and project to cortico-limbic and motor structures (A9 and A10 dopamine pathways). Electrophysiological studies on rodent or non-human primates have shown that these dopamine neurons are silent or spontaneously active. The spontaneously active neurons show slow regular firing, slow irregular firing or fast bursting activity. In the first section, we will review how neuronal firing is modulated by intrinsic factors, such as impulse-regulating somatodendritic dopamine autoreceptors, a balance between inward voltage-gated sodium and calcium currents and outward potassium currents. We will then review the major excitatory and inhibitory pathways that play important roles in modulating dopamine cell excitability. In the second section, we will discuss how, in addition to being modulated by intrinsic and synaptic factors, excitability of dopamine neurons can also be modulated by life experiences. Dopamine neurons change their firing rate throughout the developmental period, their activity can be modified by stressful life events, and the firing mode can change as a consequence of acute or repeated exposure to psychoactive drugs. Finally, these cells change their firing pattern in response to behaviorally relevant stimuli and learning experiences. We will conclude by discussing how changes in the physiology of the dopamine neurons could participate in the development or exacerbation of psychiatric conditions such as drug addiction.