Walking and Talking (1996) led to roles in larger studio films such as the Scream trilogy (1996, '97 and '99), but Schreiber came back to indies with The Daytrippers (1997) before returning to higher-profile fare with A Walk on the Moon and The Hurricane (both 1999). He topped off the year with an Emmy nod for his portrayal of a young Orson Welles in the HBO movie RKO 281.
The new millennium found Schreiber starring in the TV biopics Young Dr. Freud (2002) and Hitler: The Rise of Evil (2003) before taking on his most critically acclaimed role yet in a remake of The Manchurian Candidate (2004) and starring with Naomi Watts in The Painted Veil (2006).