Atheism is the deviation from integrity and the denial of the existence of God Almighty, monotheism and Islam. Even though that man has been created with the pure nature of Islam, he might incline to atheism because of some reasons and motives. However, the phenomenon of atheism was available at the time of the Ahlul-Bayt (peace be on them), but its general characteristics, at that time, were sensualism and naturalism, and that knowledge was limited to senses, imagination, and rationality tainted by illusion and imagination, emphasizing mans physical aspects. Heretics and atheists denied the existence of the Creator, after denying the creation of the possible world, making use of imaginary and illusory reason. The Ahlul-Bayt (peace be on them), as being the scientific reference then, responded to atheism at their time in many ways, in order to undertake their duty of guiding humanity toward perfection. In this task, the Infallible Imams (peace be on them) followed ethical and rational methods. By ethical methods, we mean giving the chance to atheists to ask questions and offer their suspicions, without criticizing an atheist’s personality, but his arguments. Rational methods, both conceptual and contextual, can be summarized into the provocative approach, avoiding of possible harm, making use of rational and logical rules, with emphasizing the principle of causality, and reasoning according to  the self arguments, quoting the proofs the human self, referring to it and establishing clear evidence by making use of empirical sciences to prove the existence of the Creator and refute atheism.