Magnetic resonance (MR) fingerprinting is a new quantitative imaging paradigm, which simultaneously acquires multiple MR tissue parameter maps in a single experiment. In this paper, we present an estimation-theoretic framework to perform experiment design for MR fingerprinting. Specifically, we describe a discrete-time dynamic system to model spin dynamics, and derive an estimation-theoretic bound, i.e., the Cramer-Rao bound (CRB), to characterize the signal-to-noise ratio (SNR) efficiency of an MR fingerprinting experiment. We then formulate an optimal experiment design problem, which determines a sequence of acquisition parameters to encode MR tissue parameters with the maximal SNR efficiency, while respecting the physical constraints and other constraints from the image decoding/reconstruction process. We evaluate the performance of the proposed approach with numerical simulations, phantom experiments, and in vivo experiments. We demonstrate that the optimized experiments substantially reduce data acquisition time and/or improve parameter estimation. For example, the optimized experiments achieve about a factor of two improvement in the accuracy of $T_2$ maps, while keeping similar or slightly better accuracy of $T_1$ maps. Finally, as a remarkable observation, we find that the sequence of optimized acquisition parameters appears to be highly structured rather than randomly/pseudo-randomly varying as is prescribed in the conventional MR fingerprinting experiments.