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The analysis of medical images has been woven into the fabric of the pattern analysis and machine intelligence (PAMI) community since the earliest days of these Transactions. Initially, the efforts in this area were seen as applying pattern analysis and computer vision techniques to another interesting dataset. However, over the last two to three decades, the unique nature of the problems presented within this area of study have led to the development of a new discipline in its own right. Examples of these include: the types of image information that are acquired, the fully three-dimensional image data, the nonrigid nature of object motion and deformation, and the statistical variation of both the underlying normal and abnormal ground truth. In this paper, we look at progress in the field over the last 20 years and suggest some of the challenges that remain for the years to come.