During the last decade, viral technologies have progressively been used in the studies of different aspects of brain functions. Relatively recently, viral techniques have been combined with optogenetics, which allows the study of modifications of the activity of different brain regions and circuits in vitro in brain slices and in behaving animals. In the vast majority of these cases, the viral/optogenetic approach has been used to manipulate the release of the classical neurotransmitters, l -glutamate, and GABA. Recently, several studies have focused on viral/optogenetic manipulation of “nonclassical” neurotransmitters—neuromodulators, primarily the biogenic amine dopamine. However, another large group of neuromodulators—neuropeptides–has as yet remained unexplored by viral/optogenetic approaches. In this chapter, we present an overview of viral and transgenic techniques applied to targeting neuropeptidergic hypothalamic neurons. We provide examples of using optogenetics for manipulating neuropeptide-expressing neurons, including our own protocols on the expression of Channelrhodopsin 2 in oxytocinergic hypothalamic neurons. Furthermore, in this chapter we provide some advice for the correct interpretation of results of optogenetically altered release of oxytocin (and potentially other neuropeptides) and perspectives of combining optogenetics with other techniques, such as functional magnetic resonance imaging (fMRI), microdialysis, and electrophysiological field recording for further exploration of neuropeptide functions in the brain.