Dopamine was first identified as a neurotransmitter localized to the midbrain over 50 years ago. The dopamine transporter (DAT; SLC6A3) and the vesicular monoamine transporter 2 (VMAT2; SLC18A2) are regulators of dopamine homeostasis in the presynaptic neuron. DAT transports dopamine from the extracellular space into the cytosol of the presynaptic terminal. VMAT2 then packages this cytosolic dopamine into vesicular compartments for subsequent release upon neurotransmission. Thus, DAT and VMAT2 act in concert to move the transmitter efficiently throughout the neuron. Accumulation of dopamine in the neuronal cytosol can trigger oxidative stress and neurotoxicity, suggesting that the proper compartmentalization of dopamine is critical for neuron function and risk of disease. For decades, studies have examined the effects of reduced transporter function in mice (e.g. DAT‐KO, VMAT2‐KO, VMAT2‐deficient). However, we have only recently been able to assess the effects of elevated transporter expression using BAC transgenic methods (DAT‐tg, VMAT2‐HI mice). Complemented with in vitro work and neurochemical techniques to assess dopamine compartmentalization, a new focus on the importance of transporter proteins as both models of human disease and potential drug targets has emerged. Here, we review the importance of DAT and VMAT2 function in the delicate balance of neuronal dopamine. This review describes the importance of the dopamine transporter (DAT) and the vesicular monoamine transporter 2 (VMAT2) on dopamine compartmentalization and neuronal health (A–C). While theoretical, this schematic highlights emerging evidence from mouse models of varying transporter levels. We predict that the continuum of transporter function in these animal models will allow for new discoveries concerning endogenous dopamine handling, pharmacological manipulation of the transporters, and dopamine‐dependent behaviors (D).