The inhibitory neurotransmitter, GABA, is a low-molecular-weight molecule that can achieve many low-energy conformations, which are recognized by GABA receptors and transporters. In this article, we assess the structure-activity relationship profiles of GABA analogs at the ionotropic ρ GABA(C) receptor. Such studies have significantly contributed to the design and development of potent and selective agonists and antagonists for this subclass of GABA receptors. With these tools in hand, the role of ρ GABA(C) receptors is slowly being realized. Of particular interest is the development of selective phosphinic acid analogs of GABA and their potential use in sleep disorders, inhibiting the development of myopia, and in improving learning and memory.