This book systematically develops the theory of generalized locally Toeplitz (GLT) sequences and presents some of its main applications, with a particular focus on the numerical discretization of differential equations (DEs). It is the first book to address the relatively new field of GLT sequences, which occur in numerous  scientific applications and are especially dominant in the context of DE discretizations. Written for applied mathematicians, engineers, physicists, and scientists who (perhaps unknowingly) encounter GLT sequences in their research, it is also of interest to those working in the fields of Fourier and functional analysis, spectral analysis of DE discretization matrices, matrix analysis, measure and operator theory, numerical analysis and linear algebra. Further, it can be used as a textbook for a graduate or advanced undergraduate course in numerical analysis.