19F NMR offers exceptional insights for diverse physiological and pharmaceutical investigations. High sensitivity and lack of interfering background signal in the body have enabled the observation of exogenously administered agents and their metabolites. 19F exhibits a large chemical shift range, which is exquisitely sensitive to the microenvironment. In addition to chemical shift, relaxation processes (R1 and R2), and chemical exchange may be tailored to be responsive to a parameter of interest such as pO2, pH, metal ion concentrations, transgene/enzyme activity or hypoxia. I will review 19F NMR/MRI as a foundation for diverse applications and recent innovations.