According to all we know about human civilisation, different cultures started reflecting on the nature of knowledge and truth about 2500 years ago. This knowledge of knowledge, or epistemology, is one of the major disciplines in academic philosophy. It is a central part of philosophy of science and science theory. Entire library shelves are filled with elaborations on this topic. Admittedly, it is not necessary for a scientist to study and know all this theory. Yet, a bit of it – the quintessential conclusion, perhaps – will surely make the chemical scientist and researcher a better practitioner. Therefore, this chapter attempts to introduce epistemology in a nutshell: what is knowledge, truth and meaning, what is science able to contribute, and when should the chemist be aware of limits and pitfalls of scientific knowledge? The practical relevance for the conduct of chemical science and its application in industry and innovation shall guide a short tour through this complex topic. It is not a co-incidence or stylistic choice that the key themes below are questions. It is notoriously difficult to settle epistemological debates with definite answers. It may be unsatisfying for chemists, but this chapter's main goal is to raise awareness of questions that challenge beloved convictions and comfort zones. The result is more careful practice in scientific inquiry, and a reasonable balance between epistemic humbleness and confidence, that means knowing the strengths and limits of scientific knowledge.