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This essay deals with four main topics: the notion of philosophical psychology; the idea that physical events and mental events cannot be compared to one another; psychophysical mechanism; and the theory of local signs. These are all key elements in the Medicinische Psychologie of Rudolph Hermann Lotze (1817‒1881). By philosophical psychology, Lotze understands not only the collection of experimental data regarding physiological and mental states but also their philosophical processing outlining an interpretation of the real nature of the mind‒body connection. Within this framework, Lotze introduces the psychophysical mechanism as based on a key philosophical idea: mind and body are incomparable, but, nevertheless, they are in reciprocal relation (Wechselwirkung). In virtue of said special relation, movements that take place in the mental sphere of reality are transferred or translated in the bodily sphere and vice versa. This rearrangement (Umgestaltung) from one sphere of reality to the other is termed by Lotze “transformation to equivalent.” Through the concept of equivalence, Lotze supports the idea that the mind and the body form an organic whole. However, psychophysical mechanisms should not be seen as not a fixed series of physical changes followed by an equally fixed series of mental changes: physical changes are “read,” organized, and then transformed by the mind into something purely mental. This, in turn, produces new mechanical force and more physical changes. Lotze's legacy and long‐term impact is finally read against the background of his contributions.