This chapter explores the physics behind defining zero and coming to grasp with the physical conception of nothing or emptiness. This issue is a moving target as technology has improved our ability to measure increasingly small and faster phenomena. The real limit as to what zero means in physics is not solely instrumental detection, but rather limits based on theoretical extrapolations derived from existing models. There are many physical phenomena where the void or zero play a role; is truly empty space possible, what is the lowest temperature that can exist, is there a zero time? Physics provides insight into addressing these issues since its goal is to define the framework of the universe. This chapter provides a definition of the different scales of matter and space ranging from quantum to atomic to microscopic to macroscopic to cosmic scales, and discusses why laws and theories applicable to one scale may not be applicable to another. One must define a perspective or frame of reference as to how to interact with nature relative to the definition and properties of particles and matter. Defining this framework or context is important in the application of zero in later chapters.