The current pattern of slip(1,2) within the San Andreas fault system in the San Francisco Bay area is distinctly different from the long-term slip pattern inferred from the geological record(3,4). This difference is not surprising because geological data record the accumulated displacements over many earthquake cycles, whereas geodetic data reveal the present-day slip pattern. It is not known, however, what mechanism triggers the change from the ’interseismic’ slip pattern (when the San Andreas fault is locked) to the ’co-seismic’ slip pattern (when the San Andreas fault ruptures in earthquake slip). Here we use numerical simulations of the entire seismic cycle on this complex fault system to show that the San Andreas fault may be in a critical state and sensitive to small perturbations in regional compression. In particular, we find that small increases in regional compression may lock the San Andreas fault, whereas small decreases in regional compression may release the locked segment and so permit co-seismic slip. This sensitivity suggests that cyclic changes in the regional stress field resulting from plate convergence and thrust faulting in the Coast Ranges could trigger major earthquakes on the San Andreas fault.