The aim of this paper is to develop foundations of umbral calculus on the space D of distributions on R d , which leads to a general theory of Sheffer polynomial sequences on D . We define a sequence of monic polynomials on D , a polynomial sequence of binomial type, and a Sheffer sequence. We present equivalent conditions for a sequence of monic polynomials on D to be of binomial type or a Sheffer sequence, respectively. We also construct a lifting of a sequence of monic polynomials on R of binomial type to a polynomial sequence of binomial type on D , and a lifting of a Sheffer sequence on R to a Sheffer sequence on D . Examples of lifted polynomial sequences include the falling and rising factorials on D , Abel, Hermite, Charlier, and Laguerre polynomials on D . Some of these polynomials have already appeared in different branches of infinite dimensional (stochastic) analysis and played there a fundamental role.