Opioids are the most potent analgesics. However, their clinical use is limited by side effects like respiratory depression and their high potential for abuse. In addition, they modulate immune functions and cause immunosuppression. Effects of clinically important opioids like morphine are mediated by the mu-opioid receptor. Knowledge about the mechanisms controling the expression of the mu-opioid receptor gene in neuronal and immune cells is crucial to understand the dynamics and the activity of this receptor. Cytokines, mediators typically released from cells of the immune system, are potent regulators of mu-opioid receptor gene expression. This emphazises the importance of mu-opioid receptors in the neuro-immune-crosstalk and their role as a molecular basis for such interactions. In this review, the up-regulation of human mu-opioid receptor gene expression in neuronal and immune effector cells by interleukin-1, interleukin-4, interleukin-6 and tumor necrosis factor, as well as its down-regulation by interferon-gamma and granulocyte/macrophage colony-stimulating factor will be summarized along with molecular mechanisms, such as transcription factor-promoter-interactions. In addition, the physiological importance of these regulatory events will be discussed.