Alkali metals, especially sodium and potassium, are plentiful and vital in biological systems. They take on important roles in health and disease. Such roles include the regulation of homeostasis, osmosis, blood pressure, electrolytic equilibria, and electric current. However, there is a limit to our present understanding; the ions have a great ability and capacity for action in health and disease, much greater than our current understanding. For the regulation of physiological homeostasis, there is a crucial regulator (renin-angiotensin system, RAS), found at both peripheral and central levels. Misregulation of the Na(+)-K(+) pump, and sodium channels in RAS are important for the understanding of disease progression, hypertension, diabetes, and neurodegenerative diseases, etc. In particular, RAS displays direct or indirect interaction important to Parkinson's disease (PD). In this chapter, the relationship between the regulation of sodium/potassium concentration and PD was sought. In addition, some recent biochemical and clinical findings are also discussed that help describe sodium and potassium in the context of traumatic brain injury (TBI). TBI is caused from the heavy striking of the head; this strongly affects ion flux in the affected tissue (brain) and damages cellular regulation systems. Thus, inappropriate concentrations of ions (hyper- and hyponatremia, and hyper- and hypokalemia) will perturb homeostasis giving rise to important and far reaching effects. These changes also impact osmotic pressure and the concentration of other metal ions, such as the calcium(II) ion.