  This article is an introduction to independence, interpretability, large cardinals and their interrelations.  Section 1 surveys the classic independence results in arithmetic and set theory.  Section 2 introduces the interpretability hierarchy and describes some of its basic features.  Section 3 introduces the notion of a large cardinal axiom and discusses some of the central examples.  Section 4 brings together the previous themes by discussing the manner in which large cardinal axioms provide a canonical means for climbing the hierarchy of interpretability and serve as an intermediary in the comparison of systems from conceptually distinct domains.  Section 5 briefly touches on some philosophical considerations. 