The two main topics emphasized in this book, special functions and fractional calculus, are currently under fast development in theory and application to many problems in statistics, physics, and engineering, particularly in condensed matter physics, plasma physics, and astrophysics. The book begins by setting forth definitions, contours, existence conditions, and particular cases of the H-function. The authors then deal with Laplace, Fourier, Hankel, and other transforms. As these relations are explored, fractional calculus and its relations to H-functions emerge with important results on fractional differentiation and fractional integral operators.The latter chapters explore applications of H-functions in statistical distribution theory, structures of random variables, generalized distributions, Mathai's pathway models, and versatile integrals. The authors also present an introduction to functions of matrix argument, with special focus on the space of Hermitian positive matrices. The book concludes with the most recent applications of H-functions and fractional calculus to physical problems in reactions, diffusion, reaction-diffusion theory, statistics, superstatistics, and generalized entropies.