In this lecture we will look at how to approach the challenge of diagnosing and treating immune-mediated polyarthritis in practice. We will consider important differentials and how to structure diagnostic investigations to achieve a correct diagnosis. In addition, we will discuss options for treatment and challenges associated with long-term management. Using a combination of relevant theory, scientific literature and case examples, this lecture will aim to provide clinicians with increased understanding and confidence to investigate and manage these cases in practice.