An inertial frame of reference is defined as a frame that is not accelerating, which relates directly to Newton's first law of motion. While perfect inertial frames may not exist due to gravitational influences, practical examples include a frame relative to a point on Earth's surface. In space travel, the sun can serve as a reference point for position, while distant stars can help establish direction. Understanding the nuances of inertial frames can clarify their application in physics. This foundational concept is essential for grasping motion and forces in various contexts.