Recent efforts are beginning to explore the application of extracorporeal shock wave therapy (ESWT) to near lung tissue and transcranial indications. This is driven by a desire to expand the well establish therapeutic and regenerative benefits to a new group of patients. Through mechanotransduction of the incoming pressure pulse, a cascade of biochemical responses is triggered within the cells. Simultaneously, there is a non-linear response in the physical bulk properties of the targeted structures. Either one of those processes may be both beneficial or detrimental for the treatment outcome. We present findings on the efficacy of expanding ESWT to these areas currently consider counterindications. Treating near lung or brain tissue using low energy shockwaves holds an unlocked regenerative potential but has to be seen in the light of potentially destructive tensile forces imparted on the tissue. Based on reference measurements, computational simulations, and in-vivo experiments we explore competing considerations in moving towards a clinical use of ESWT in the potential treatment of a wide range of new indications.