Bacterial chondronecrosis with osteomyelitis (BCO) is a leading cause of lameness in broiler chickens, which results in financial losses due to mortality and reduced growth. Due to the nature of the condition, it raises animal welfare and food safety concerns as well. The pathology in the commercial setting is derived from a combination of weak bone and bacterial translocation and infection. Multiple genetic, nutritional, and managerial strategies have been employed to help mitigate the negative consequences of BCO; however, without understanding of the underlying causes of onset and progression, any benefit of these interventions is likely tempered. Compounding our dearth of knowledge is the fact that current methods of identification rely on subjective gait scores for lameness that may not show changes until the problem is severe or require diagnosis of BCO at necropsy. Therefore, our research group has aimed to tackle both facets of this important poultry concern. Here, we highlight several of our recent findings regarding the proteomic signature of BCO bone, as well as two potentially non-invasive assessment tools, dual energy x-ray absorptiometry and computed tomography, that can aid in future study. Together, we believe that this information provides the framework for future investigations and for subsequent development of mechanism-based strategies to prevent this pathology as well as better tools to impact genetic selection against BCO.