We present the first general analysis of New Physics contributions to the D0-D[over ](0) lifetime difference (equivalently DeltaGamma(D)). We argue that New Physics (NP) contributions to |DeltaC|=1 processes can dominate the lifetime difference in the flavor SU(3) limit. We provide several specific examples of models that produce sizable effects in DeltaGamma(D) for realistic values of light quark masses, even if such NP contributions are undetectable in the current round of D0 decay experiments. This makes DeltaGamma(D) a viable observable for studies of indirect effects of New Physics.