This text offers a synthesis of theory and application related to modern techniques of differentiation. Based on undergraduate courses in advanced calculus, the treatment covers a wide range of topics, from soft functional analysis and finite-dimensional linear algebra to differential equations on submanifolds of Euclidean space. Suitable for advanced undergraduate courses in pure and applied mathematics, it forms the basis for graduate-level courses in advanced calculus and differential manifolds. Starting with a brief resume of prerequisites, including elementary linear algebra and point set topology, the self-contained approach examines liner algebra and normed vector spaces, differentiation and calculus on vector spaces, and the inverse- and implicit-function theorems. A final chapter is dedicated to a consolidation of the theory as stated in previous chapters, in addition to an introduction to differential manifolds and differential equations.