γ-Amino butyric acid (GABA(B)) receptors are heterodimeric G protein-coupled receptors expressed throughout the central nervous system in virtually all neurons. They control the excitability of neurons via activation of different downstream effector systems in pre- and postsynaptic neurons and as such regulate all major brain functions including synaptic plasticity, neuronal network activity, and neuronal development. Accordingly, GABA(B) receptors have been implicated in a variety of neurological disorders and thus are regarded as promising drug targets. A key factor determining the extent of GABA(B) receptor-mediated inhibition is the level of receptors at the cell surface available for signaling. There is increasing evidence that cell surface expression of functional GABA(B) receptors is affected in neurological diseases. This diminishes inhibitory control of neuronal excitation and may contribute to the disease state. Here, we discuss recent findings on mechanisms involved in regulating cell surface expression of GABA(B) receptors in addiction, neuropathic pain, and brain ischemia.