The placebo effect is a fascinating yet puzzling phenomenon which has challenged investigators over the past 50 years. Some researchers have initiated investigations of the effects of placebos in animals, and have shown that associative learning is a major way to elicit placebo responses. Pain is the field in which most of the placebo research has been performed. In contrast to numerous studies involving human subjects, the available literature on placebo-induced analgesia in animal models is rare. This chapter introduces a special drug-conditioning procedure, a cue paired with morphine or aspirin, eliciting analgesic responses in a hot plate test. This established placebo analgesia was considered to be transferable from pain to depression and could produce a significant antidepressant effect in a test on depression in mice. Furthermore, the opioid placebo analgesia was found to be mediated exclusively through a μ-opioid receptor in the rat. The pros and cons of studying placebo in animal models are also discussed at the end of this chapter.