Immune-mediated polyarthritis (IMPA) is a common disease process in the dog.(1) The immune-mediated polyarthropathies are divided into two major categories: erosive (or deforming) and nonerosive (or nondeforming). Understanding the pathophysiology of the immune attack on affected joints is paramount in choosing the most effective therapy for managing canine IMPA. This review article is the first of a two-part series and focuses on the pathophysiology of IMPA. The second article in this series, to be published in the March/April 2012 issue, concentrates on the diagnosis and treatment of immune-mediated polyarthritis.