The discussion becomes more complex when living matter enters the picture. Life can be defined as what distinguishes animals and plants from inorganic matter, including the capacity for movement, reproduction, growth, thought, and development preceding death. Living organisms have the ability to fight entropy, which would drive them to be in equilibrium with their environment, an intriguing definition of death. These are broad definitions, but they help define concepts such as the absence of life or zero biological effects after low-level chemical exposure. The molecular and cellular interactions that can occur between a chemical and biological structure form the basis for determining the nature of the dose-response relationship. Topics to be discussed in this chapter range from molecular to cellular biology, to the anatomy and physiology of complex multicellular organisms, and the parameters used to define a biologically active dose. An organism is a large network of individual cells and organs with numerous receptors, often responsive to the same molecules, but producing a myriad of effects at different concentrations and locations. What are the roles that diffusing across membranes and dilution play in determining a biologically relevant exposure? Finally, how is a zero biological effect quantitated?