Behavior is shaped by a variety of genetic and epigenetic mechanisms, including those underlying anxiety and fear. Neuropeptides are ideal candidates to be involved in the regulation of emotional facets as they are released within the brain and act as neuromodulators/neurotransmitters; furthermore, their large number is prone to direct changes by mutations. A variety of approaches have been used to reveal the physiological involvement of neuropeptides in anxiety-related behavior, including those focused on behavioral effects of neuropeptides and, vice versa, the influence of behavioral phenomena on intracerebral neuropeptides. In concert with other neuropeptides and classical transmitters, particularly CRH and vasopressin are promising candidate neuropeptides to determine not only the activity of the hypothalamopituitary-adrenocortical axis, but also anxiety-related behavior including its cognitive components. CRH and vasopressin interactions with specific receptor subtypes have been shown to induce consequences on emotionality, and CRH and vasopressin responses to both anxiogenic stimuli and extreme levels of inborn anxiety confirm their critical involvement in normal and pathological anxiety. Based on behavioral and neuroendocrine data obtained from proper animal models, the neurobiological and genetic analyses of anxiety and fear will provide the prerequisites to develop novel and more causal therapeutic strategies for anxiety disorders.