Some embodiments of an infusion pump system include an occlusion detection system to detect when an occlusion exists in the fluid path between the medicine reservoir and the infusion site located, for example, on the user's skin. The occlusion detection system can be configured to self-calibrate in a manner that accounts for changes in environmental conditions, such as ambient temperature, pressure, or the like, so that the occlusion detection system provides reliable feedback to a user as to the occluded or non-occluded state of the medicine flow path.