An inertial frame of reference is defined as one where an object remains at rest or in uniform motion unless acted upon by a force, while a non-inertial frame involves acceleration or changes in direction. In Newtonian mechanics, the frame of the Earth's surface is approximately inertial, whereas frames tied to accelerating objects, like a subway car, are non-inertial. In general relativity, local inertial frames are defined by free-falling observers, and gravity can be considered a fictitious force in this context. The distinction between fictitious and real forces becomes blurred in general relativity, as forces like gravity are redefined based on proper acceleration. Understanding these concepts is crucial for grasping the complexities of motion in both Newtonian and relativistic physics.