Methods and systems for detecting defects on a wafer using defect-specific information are provided. One method includes acquiring information for a target on a wafer. The target includes a pattern of interest formed on the wafer and a known DOI occurring proximate to or in the pattern of interest. The information includes an image of the target on the wafer. The method also includes searching for target candidates on the wafer or another wafer. The target candidates include the pattern of interest. The target and target candidate locations are provided to defect detection. In addition, the method includes detecting the known DOI in the target candidates by identifying potential DOI locations in images of the target candidates and applying one or more detection parameters to images of the potential DOI locations.