Set in New York City in the late forties, Shadows on the Hudson presents the inter-twined lives of a group of prosperous Jewish refugees. Boris Makaver is the center of the circle, a pious and wealthy businessman. His greatest trial is his daughter, Anna, unlucky in her choice of husbands. Married first to Yasha Kotik, a lunatic actor, and then to a hapless, unemployed attorney, she plans to escape with Hertz Grein, a man torn between ascetic yearnings and romantic entanglements.

Amid family quarrels and religious debates, marriages of love and convenience are attempted and abandoned, lovers separate, and spouses die or even manage to return from the dead.