Anxiety is a common human emotional experience that causes decreased quality of life and increased social burden worldwide. However, the treatment options currently available for anxiety are limited as the molecular mechanisms of these complicated emotional disorders are poorly understood. With the development of integrative methods including genetic manipulations, a variety of molecular targets involved in anxiety have been revealed, from membrane receptors, such as 5-HT receptor, GABA(A) receptor and GluR5 kainate receptor, and intracellular signaling proteins, such as CaMKIV and AC8, to transcription factors, such as CREB and Egr-1. We propose that all these molecules act together to form a balance between excitatory and inhibitory transmission that is critical for physiological anxiety, and that prolonged disturbance of any of them can promote pathological anxiety-like behavior. Studies on the interactions between these molecules will help elucidate the cellular mechanisms of anxiety, and will provide molecular targets for treating the disorders.