More than a century ago, experimental work and clinical observations revealed the functional communication between the brain and the peripheral immune system. This is documented on the one hand by studies firstly demonstrating the effects of catecholamines on the circulation of leukocytes in experimental animals and humans and on the other hand via the work of Russian physiologist Ivan Petrovic Pavlov and his co-workers, reporting observations that associative learning can modify peripheral immune functions. This work later fell into oblivion, since little was known about the endocrine and immune system’s function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses. In this article, we embark on a fascinating exploration of the historical trajectory of behaviorally conditioned immune responses. We'll pay homage to the visionary scientists who laid the groundwork for this field of research, tracing its evolution from early theories of how associative learning can affect immunity to the modern-day insights that behavioral conditioning of pharmacological responses can be exploited to improve the efficacy of medical interventions for patients.