Currently, physics plays a central role in medicine, imaging diagnostics, and in oncology, radiotherapy and hadron therapy, photodynamic therapy or photochemotherapy, oncological hyperthermia, thermal ablation, electrochemotherapy (ETC), and irreversible electroporation (IRE), ending with tumor treating fields (TTF). The immune system consists of a very complex cellular structure which, thanks to soluble elements and strict cell-cell connections, creates interactions between cells but also with cells which are part of other organs and systems. This network is the principal coordinative structure that enables the immune system to maintain its dynamic equilibrium (homeostasis) thanks to signals with activation or inhibitory function and, in the meantime, to adapt its actual response to stimuli coming from the environment. When evaluating the possible connection between an electromagnetic source and the biological effects induced by it, it is very important to take into account all of the different regions which are part of the electromagnetic spectrum. The type of the interaction with a biological substance is determined by the frequency or wavelength of the source, the waveform, the amplitude of the signal, the exposure time, a series of electrical parameters characteristic of the signal, as well as the geomagnetic field and, in general, from the environment in which the electromagnetic field (EMF)EMFElectromagnetic field (EMF) is applied. Furthermore, the response of human cells to EMFs also depends on their specific characteristics, such as type, metabolic activity, and physiological function. Given that the immune system has a fundamental role in the control of various pathologies and in the growth of tumors, a lot of laboratories have developed an interest in extremely low-frequency electromagnetic field (ELF-EMF)ELF-EMFExtremely Low Frequency Electro-Magnetic Fields (ELF-EMF) stimulation on different cell types and processes. Furthermore, some other authors have focused on the effects that ELF-EMFs have in terms of expression of specific genes and in terms of signal transduction pathways, although, to date, the experimental data derived from these studies seem to be quite controversial. Therefore, we wanted to carry out a review of the literature aimed at analyzing and clarifying the biological effects and the relative therapeutic significance of ELF-EMF.