A Null Pointer Exception occurs in programming when a program attempts to use an object reference that has not been initialized or is set to null. This means the program is trying to access or manipulate data that doesn't exist, leading to a runtime error. It is a common issue in languages like Java and C#. To prevent a Null Pointer Exception, developers can implement checks to ensure that an object is not null before using it. This practice helps maintain the stability of the program and improves overall code quality, making it easier to debug and maintain.