Murine osteoarthritis (OA) models are important for exploring OA pathology and treatment in the pre-clinical study. Longitudinal <i>in vivo</i> imaging modalities, including X-ray, computed tomography and magnetic resonance imaging, are commonly used diagnostic tools in OA clinic, while end-point histomorphometry analysis is the major outcome measurement in pre-clinical study because clinical imaging modalities have limited resolution for small animals. Thus, developing new longitudinal <i>in vivo</i> imaging protocols for murine models of OA is a critical unmet need. Here, commonly used post-traumatic murine models of OA and the utilization of X-ray, computed tomography and magnetic resonance imaging techniques to monitor disease progression and treatment response in these models is reviewed. Then ultrasound (US) imaging, a widely used and cost-efficient tool, in arthritis clinic and its utilization in knee OA of patients is introduced. Finally, our experience of using US imaging in normal and OA mouse knees is described to demonstrate the feasibility of US as a new imaging tool to measure disease progression longitudinally.