Clinical biophysics is an interdisciplinary scientific area that utilizes methods and theories from physics to analyze biological systems and examines the interaction between nonionizing physical stimuli and biological systems, focusing on how these interactions alter their behavior. Clinical biophysics integrates the core principles and methodologies of pharmacological research. It specifically focuses on studying the different parameters of physical agents, investigating their mechanisms of action and the metabolic pathways they engage in, and evaluating their application in treating relevant pathological conditions. Clinical biophysics is based on a new pharmacology that employs physical stimuli for the treatment of various human pathologies. This process, known as “biophysical stimulation,” involves biological effects that are influenced by specific physical parameters, including the frequency, amplitude, waveform of the signal, and the duration of exposure. According to new pharmacology, the effects of physical agents should be described in terms of how they modulate cellular functions, which forms the basis for their clinical use. The cell membrane has been identified as the primary target and site of interaction for biophysical stimulation. A major tool in this therapeutic landscape is represented by pulsed electromagnetic fields (PEMF) that are yet commonly used for bone and cartilage stimulation and are still under investigation for muscle and tendon application. In all these fields results are promising both in vitro and in vivo. The differences in physical parameters for treating different pathological settings dictate the selectivity and specificity of actions allowing for detailed programs for each clinical picture, but some recent intuitions suggest that a common mechanism of action may reside in the activation of very early common developmental pathway by PEMF exposure. Through the interaction with adenosine receptors and, likely, other mechanoreceptors at the cell surface, early developmental pathways are triggered, i.e., protooncogenes as c-fos, and specific anabolic patterns of differentiation are expected to be strongly conditioned by the extracellular environment that surrounds the cells. Thus, PEMF may be conceived not as a mere unrealistic “one size fit for all” clothing but as an efficient and promising therapeutic tool that, following different and specific parameters for each tissue, allows for a specific anabolic pathway driven by the activation of early differentiative stimuli in the cell metabolism coupled with the interaction with the surrounding unique extracellular space. In this chapter, an overview of the PEMF mechanism of action and the recent preclinical and clinical studies are presented for osteo/cartilaginous, muscular, and tendon lesions, leading the readers to the vast and fascinating landscape of PEMF, showing their promising potential in treating orthopedic pathologies.